Global Regulatory Monitor
Regulatory News, Week 4 · 2026/7

Complaint records are deficient in that they do not include the findings ofthe investigation and follow-up.

Specifically, A. Your firm failed to adequately investigate customer complaints that were received as Adverse Events. The following adverse events were reviewed and deemed inadequate; this is not an exhaustive listing: i. Complaint# 1406005 opened on 08/03/2025 as an Adverse Event and critical complaint. Customer found a shard of metal in the ointment that was on their®®. The product was(b) (4) (6)(4) NNN Ointment 149, Lov! (BYKAYI Expiration (b) (4) ii. Complaint# 1285238 opened on 12/20/2023 as an Adverse Event. Customer stated they immediately felt a burning, intense itching, and what felt like "shards of glass," resulting in their (4) becoming (BAYT NEE: This product was (E)IC4) lll iilllllllllll = (4) Solution USP (694), Lov! (6) (4). Expiration (ON). iii. Complaint# 1269630 opened on 11/15/2023 as an Adverse Event. Customer had a severe reaction to the (8%) utilized. The product was (O)(4) (b)(4), Lot# (6)(4) Manufacturer Lot# (6) (4), Expiration ©)@). B. Additionally, your firm failed to file a Field Alert Report (FAR) for Complaint# 1329875 opened on 08/07/2024 as an Adverse Event (AE). Customer stated they noticed a "black" substance inside the (b)(4) and on the inside of

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

Specifically, A. Your operators are not following appropriate aseptic practices during active manufacturing activities. The following is not an exhaustive listing of the inadequate aseptic practices observed during the commercial manufacturing of(b) (4) Solution (6) (4) (Lot# (6) (4)) on Filling Line "*: | i. Brisk movements and walking swiftly throughout the Grade B room near the (6) (4) Filling Line (Grade A). | ii. Donning a) pair of sterile gloves and moving away from the glove donning station. We also | observed some instances where they put on one glove and held the second one as they walked away from the station and utilizing the sterile © @ pair to throw away trash. y P y | iii, While changing the environmental monitoring plates within the Grade A area of Filling Line# ™®, the operator was seen moving quickly and reaching over areas where open and exposed empty | bottles were located. iv. During an intervention ofremoving a stuck empty bottle, we observed the operator manipulate the forceps at the end that comes in contact with the open container. Additionally, the operator abruptly manipulated ajammed bottle in a matter that the bottle was flicked into the(b) (4) ()(4) ste

Written procedures are not followed for the receipt, storage and handling of.

Specifically, A. Your firm failed to document and complete the Purchasing Notification of Missing Documents Form (SOP21-076 Form B) in your locked Quarantined cage for the following incoming shipments: i. (G4) Material (GAY. Lov# (BPAY) received on 16-FEB-2026 ii. (6) (4) (Material# (b)(4) _) received on 1 1-MAR-2026 iii, = (BY) materials (Lot# (6)(4) received on 11-MAR-2026 These items have not been issued the SOP21-076 Form B. This issue was not resolved within the required time or escalated to the Warehouse and Quality Management Team as required by SOP21-076, Receiving Process, Rev. 32, Effective Date: 24- NOV-2025 section 5.5.1. which states, “If the shipment is missing the proper documentation or is incorrect or incomplete, immediately email the Sourcing and Procurement, Materials Management and Incoming Quality departments a complete copy of SOP21-076 Form B (Purchasing Notification of Missing Documents). If the issue is not resolved within(6) (4) 7 escalate the issue to the Warehouse and Quality Management team.” Your Quality Assurance Manager stated that FormB has not been filled out for all materials missing documents upon receipt and the procedure has not been followed.

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

Specifically, On 5/27/2026, the operator was observed conducting aseptic manipulations in which the movement of first air in the ISO 5 LAFH <Redacted B4> was blocked during the aseptic production of the following sterile drug products: • Sodium Phosphate 15mmgm in Dextrose 5% 100mL, Order ID: naphos052726, BUD 06/06/2026 • Cefepime 2g, Order ID: cefepime2052726, BUD: 06/11/2026 The operator's hand placement was observed blocking the bag port and needle, and vial stopper and needle. The operator's hands were positioned in a manner that obstructed the unidirectional "first air" between the HEPA filter and the critical work surface. On 5/28/2026, the operator was observed conducting aseptic manipulations in which the movement of first air in the ISO 5 LAFH <Redacted B4> was blocked during the aseptic production of the following sterile drug products: • Daptomycin (Cubicin) 750 mg/NS 50 mL, Order ID: 84305997, BUD: 05/30/2026

Personnel performed aseptic manipulations with exposed hair or skin.

Specifically, On 5/27/2026, during the aseptic production of the following drug product: • Ondansetron 8 mg, Dexamethasone 12 mg in Sodium Chloride 0.9% 50mL Order ID: 83618268, BUD 5/2712026 I observed your operator's head and face enter the ISO 5 LAFH located in the non-hazardous Oncology suite without adequate protective gowning. The skin surrounding the operator's forehead and eyes was visibly exposed and unprotected by appropriate gowning at the time of the aseptic manipulation. On 05/29/2026 during the aseptic production of the following drug products: • Roiniplostim 500 mcg/3 mL Syringe, Order ID: 83919777, BUD 5/29/2026 • Ipilimumab (Ye/voy) 50 mg in Sodium Chloride 0.9% 100 mL, Order ID: 84304960, BUD 5/29/2026 • Nivolumab 180 mg in Sodium Chloride 0.9% 82 mL, Order ID: 84304861, BUD 5/29/2026

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

Specifically, On 06/02/2026, during aseptic production operations, an operator was observed moving quickly within ISO 5 LAFH <Redacted B4> while performing aseptic manipulations. At the time of the observation, the operator had an exposed, filled syringe of sterile drug product in hand. Rapid personnel movement within the ISO 5 critical zone is likely to disrupt unidirectional (first air) airflow, thereby compromising the sterile air barrier protecting exposed drug products and critical sites from potential inicrobial and particulate contamination. The following drug products were being aseptically produced at the time of this observation: • Daptomycin 750 mg in Sodium Chloride 0.9% 50 mL, BUD 06/04/2026, Order ID: 84305998 • Sodium Bicarbonate 8.4 % 150 mEq in Dextrose 5% 1000 mL, BUD: 06/03/2026, Order ID: 84327268

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

Smoke studies were inadequately performed under dynamic conditions.

Specifically, your firm failed to adequately perform smoke studies under dynamic conditions to demonstrate unidirectional airflow, simulate aseptic production, simulate worst-case conditions including all components, materials, and equipment present during actual or routine aseptic operations, and an adequate air quality environment within your ISO 5 critical areas.

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

Specifically, your operator failed to disinfect the <Redacted B4> machine between aseptic production operations. For example: On 5/27/2026 during the aseptic production of the following drug products, the operator failed to disinfect the <Redacted B4> machine between aseptic production operations: • Sodium Phosphate 15mmol in Dextrose 5% 100mL, Order ID: naphos052726, BUD06/06/2026 • Cefepime 2g, Order ID: cefepime2052726, BUD: 06/11/2026 On 5/28/2026, during the aseptic production of the following drug products, the operator failed to disinfect the <Redacted B4> machine between aseptic production operations: • Daptomycin (Cubicin) 750 mg in Sodium Chloride 0.9% 50 mL, Order ID: 84305997, BUD:05/30/2026

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

Specifically, observations include, but are not limited to, the following: • Peeling and Chipped Paint -Non-Hazardous Oncology Pharmacy SCA-Peeling and chipped paint was observed on both side of the door frame and surrounding walls of the non-hazardous Oncology Pharmacy Segregated Compounding Area (SCA). This room contains an ISO 5 classified LAFH used to produce sterile drug products. • Protruding Sprinkler Head -In-Patient Pharmacy ISO 7 Classified Cleanroom (Hazardous)-A protruding sprinkler head was observed in the ceiling of the In-Patient Pharmacy ISO 7 classified cleanroom used to produce sterile hazardous drugs. The sprinkler head is located directly above the ISO 5 classified LAFH. The sprinkler head is not on a routine cleaning schedule and the date of last cleaning is unknown.

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

Specifically, your firm's media fill protocol does not closely simulate the manipulations, container/closure configurations, or fill volumes used during actual production operations. For example, • During actual production, operators use syringe(s) to admix drug product into prefilled bags, sometimes changing the <Redacted B4> between each product addition. However, during media fill simulations, the operator aliquot <Redacted B4> of media and transfer it between <Redacted B4> bags <Redacted B4> dispensing into <Redacted B4> vials for incubation. • During media fill simulations, operators dispense approximately <Redacted B4> of media into <Redacted B4> vials for incubation which does not represent final fill volume of your firm's sterile drug products. However, during actual production operations, operators fill prefilled bags (ranging from <Redacted B4>) or syringes.

Materials were exposed to lower than ISO 5 quality air.

Specifically, on 5/28/2026, I observed sterile wipes stored on a counter across from ISO 5 LAFH <Redacted B4> within the ISO 7 classified cleanroom. The wipes were opened and exposed to ISO 7 air quality and were subsequently used to clean and disinfect the surfaces of the ISO 5 LAFH. According to staff, the wipes are stored in the ISO 7 environment until contents are fully depleted. Drug products aseptically produced on 5/28/2026 include but are not limited to • Daptomycin (Cubicin) 750 mg/NS 50 mL, Order ID: 84305997, BUD: 05/30/2026 • Cefepime/Sodium Chloride 0.9% 50 mL, Batch: 052826FS1, BUD: 06/12/2026 • Bumetanide 3 mg in Dextrose 5% 50 mL, Order ID: 84299952, BUD: 05/29/2026 • Acyclovir 600 mg in Sodium Chloride 0.9% 250 mL, Order ID: 84301319, BUD: 05/29/2026 • Iron Dextran 975 mg in Sodium Chloride 0.9%, Order ID: 84301224, BUD: 05/28/2026 On 5/29/2026, I observed sterile wipes stored in a cart adjacent to the ISO 5 LAFH in segregated compounding area (SCA) in the Oncology Pharmacy Suite. The wipes were opened and exposed to unclassified air and were subsequently used to clean and disinfect the surfaces of the ISO 5 LAFH. According to staff, the wipes are stored in the SCA

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

Specifically, Investigations initiated and performed by your Quality Unit in response to laboratory investigation reports (OOS) and Quality Incident Reports (QIR) for drug products, are not always comprehensive to determine all potential root causes. Additionally, Corrective and Preventive Actions (CAPAs) as a result of investigations are not always comprehensive to address root causes or adequately documented to have been performed. For Example, A. The firm's out-of-specification (OOS) investigations forg@ system failures consistently lack adequate documentation of definitive conclusions and systematic follow-up actions. For example: -OOS 2025-032 (TAMC failure: ID Microbacterium phyllosphaerae), opened April 22, 2025: Investigation closed

Document control procedures under Quality Unit oversight are inadequate.

Specifically, During our walkthrough on September 15, 2025, we observed discarded cGMP records in your outside trash bins, QC laboratory waste bins, and QA office shred bins which appear to be cGMP-controlled records. Your document control procedures do not detail record discard and/or shredding operations and which records are permitted to be discarded. The firm's current document control procedures fail to establish adequate protocols for the proper disposal ofcGMP records, including criteria for determining which records may be discarded and appropriate disposal methods for different types of controlled records. Examples of these improperly discarded records observed during our walkthrough are listed below. A. Records found in outside trash bins are as follows: -Finished Product Specification (FPS) form for batcho@ printed in error and discarded without proper documentation. -Master Manufacturing Record for ® ml w@ campaign, signed by QA but listing incorrect product (should have beenw@ ml), discarded without proper documentation. -Refractive index test form, printed in error and discarded without proper documentation. -Finished Product Specification (FPS) forms for O@ duplicate

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, A. During our inspection, we observed that your firm has on numerous occasions extended product shelf life without supporting stability data. For example, your firm extended the shelf life for homeopathic drug product US o@ nl batch number ®@® originally expiring @@ This batch was manufactured around August 2024 and shipped to the US market. Due to excess unsold inventory at the distributor, your firm initiated Planned Process Deviation (PPD)®@ dated m@ to extend the shelf life from )(4) tom@ Your firm completed relabeling with a new batch number ®@ _ and new expiration date ofm@ with the repackaged batch awaiting QA review atthe time of our inspection. We observed similar shelf-life extension practices during our review of QIR-177. dated®@ for@@ batch number @ and QIR-229, dated @@ for O@ batch number @@ B. Your firm packagesa variety ofo@ homeopathic drug products after receiving bulk product from contract manufacturers. While your firm performed a risk assessment dated May 12, 2025, to identify potential risks associated with qualification, packaging processes, and their impact on product quality, patient safety, and regulatory compliance, your firm has not perform

Complaint investigations under Quality Unit oversight are inadequate.

Specifically, A. Your firm failed to conduct adequate investigations for complaints involving the same product and similar adverse events. Three complaints were received for @@ reporting similar burning sensations: -CCPF-41394, dated 08/26/2024, foro@ batch number @@ with a complaint that "o@ elt like burning sensation." -CCPF-41415, dated 10/04/2024, forme batch number @@ with a complaint that the product "madeg@ burn." -CCPF-41432, dated 11/01/2024, for m@ with a complaint that the product "burned@@ ra Despite having batch numbers available for two of the complaints, the firm did not perform any testing on retain samples. The firm's conclusion that there was "no trend for this issue" was inaccurate, as all three complaints involved the same product and similar burning sensations in them@ area, with the pattern established since the first complaint on 08/26/2024.

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

Specifically, A. During the review of video footage of your Process Performance Qualification (PPQ) batchm4) (filing batches), manufacturing date 08 Jul 2022, I observed the manufacturing activities documented in Batch Manufacturing Record (BMR) are not contemporaneous and reflective of the actual activities performed. For example, 1)Fora - Step no. “Record the time at (0 ofcompounding” is documented in the BMR as 13:38. Whereas according to the video footage, this activity was completed on 13:48 2)For Bioburden and—_ Sampling — Step no. i Specification section for “Record time of sampling” is documented in the BMR as 13:48. ereas according to the video footage, this activity was completed on 13:56. B. During the review of video footages of batch a. I observed four (4) production operators working inside a small Grade B and Grade C rooms and two (2) production operators working inside a very small Grade A area (separated by 4) from Grade B) moving rapidly from one area to other areas within the room potentially creating a lot of air turbulence. Additionally, these operators were observed bending down, moving objects from one comer to another inside Grade B and Grade C areas

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

Specifically, Your Quality Unit lacks an adequate oversight on the control and management of GMP documents that are critical to ensure the sterile drug products manufactured at the site for the US market are safe and effective. For example, but not limited to: A. On 06/08/2023, I inspected one (1) out of four (4) lock and key access controlled Shred-it bins maintained by your firm. I observed your manufacturing department employees destroyed ““GMP documents” pertaining to original records and raw data by disposing inside an access controlled “Shred- it” bin located in your manufacturing area’s write-up and printing section. This section is used by your production operators to print controlled GMP documents and complete documentation activities related to manufacturing and sampling. Many of the documents recovered from this Shred-it bin were signed under “Reviewed by” and “Quality Approved by” sections and dated. The following are some examples of the original controlled GMP documents found inside the Shred-it bin

The written stability program does not assure testing of the drug product in the same container-closure system as that in which the drug product is marketed.

Specifically, (b) (4) samples charged on stability at a contractor are not “labeled and packaged” (L&P) and are not stored inside materials that are consistent with the product L&P. Based on the pictures of stability samples stored inside chambers, I observed aboutba vials charged on stability were inside a closed thick

The retention period for drug product reserve samples (except those described in 211.170(b)(2) and (3)) is deficient in that they are not retained for one year after the expiration date of the drug product.

Specifically, Your procedures Q-27 (Reference and Retention samples) and Q-40 (Commercial Product Quality Review) are deficient in that there is no mention of storing retention samples at conditions that is consistent with the product labeling. There is no mention of examining retention samples visually at least once a year for the evidence of deterioration. Additionally, your Quality Agreement withwe) holder is deficient in that there is no mention of responsibilities pertaining to the handling and annual verification of retention samples. During the current inspection, I observed that no retention samples are stored and that your firm has no dedicated area, or a room maintained at required conditions consistent with the product labeling conditions for the storage and handling of retention samples.

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.

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

Specifically, A. On 06-Jun-2023, I observed two (2) brown color objects (about 1.5 to 2 cm in length) inside a transparent ceiling light cover from the viewing window of Grade B room of conventional suite that has Grade A area separated byet andoa LAFoe controlled at Grade A. On 12-Jun-2023 upon my requests, your firm unscrewed the light cover that revealed the following issues: 1. Two (2) dead inspects resembling butterflies along with a gap of about 1 to 1.5 cm on interior of the

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 (21 CFR 211.100(a)).

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’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

Your firm failed to establish adequate written procedures for production and process control designed to assure that drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and to follow all of your written production and process control procedures (21 CFR 211.100(a) and 211.100(b)).

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)).

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

Specifically, During the inspection, we observed the following equipment cleaning deficiencies for equipment identified as having been cleaned: A. On 03/16/2026, we observed (b) (4) was being stored directly on the (b) (4) _ floor of (b) (4) while manufacturing (b) (4) Tablets USP (b) (4) Batch #(b) (4) _—_—. The (b) (4) is utilized for unloading materials from (b) (4) . B. On 03/16/2026, presence of white caked residue was observed in Capsule Machine ID #(®) (4) (Non- dedicated) product contact surfaces including cavities for encapsulation and Capsule (b) (4) ID A(b) (4) The equipment is located in Room 4° (Capsule Machine Room) and was cleaned for type “<-> cleaning (Major cleaning) on (b) (4) after manufacturing (b) (4) Capsules USP, (b) (4) Batch #(b) (4) on (b) (4) , and the equipment was issued a “Cleaned" status. C. On 03/18/2026, presence ofunknown white powder was observed inside the validation (b) (4) locations inside (b) (4) ID #(6) 4) located inside Room #”" Block & (non-dedicated equipment). The equipment was last used for manufacturing (b) (4) and (b) (4)

Established lab control mechanisms are not followed.

Specifically, During our lab walkthrough on 3/16/2026, we observed ® volumetric flasks in the volumetric flask cabinet, containing expired stock standards for both impurities and the active compound, along with their

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

1. Failing sterility tests occU1Ted when returned complaint samples of~)(4> !from the US market were tested. The sterility tests evaluated the remaining liquid inside samples retlllned for reports ofvisual contamination including mold, black specks, and discoloration on the~><4> IThe ~_c42 J container closure system is designed with a'~c4 I to protect the product remaining inside the bottle during use. Without identifying any deficiencies m the Cb> c4> I the sterility failures were attributed to inadequate handling by customers. Investigations were not timely. They were closed with no action to address the product on the market or extend the investigation to other batches ofthis product and other products made in the same environment, dilling the same time period. The investigations did not consider the manufactllling environment where these aseptic products were manufactlll·ed, which was subjected to repeated water incursion events into the aseptic manufactlll·ing areas and persistent recovery ofmold organisms. Failure to thoroughly investigate complaints and consider the environmental conditions at the time of manufactlll·ing is a repeat observation from the May 2025 warning lett

Aseptic processing ai·eas are deficient in that floors, walls and ceilings ai·e not smooth and/or hard swfaces that ai·e easily cleanable.

4 CbH 4 > Jand )(4) Jai·e used in the constrnction ofthe 1 <bX >----, \Uf\_,,J ~ Iaseptic manufacturmg ai·eas m builclin~ The(b><4> Remediation before project swnmaiy documentb 4 ____J identifies this mate1ial has a nsk of acce erated deterioration ofswfaces in contact with moisture and a:isinfectants, an inability to ensure complete decontamination, and a growing problem of maintaining sterile conditions in preparation areas. The document identifies the~> c41 ] mate1ial is not wate1proof. It is located in ai·eas that have been subject to water incursions from ramwater or utility leaks and 6 r sistent mold recoveries. No specific remediation plan to fully replace the material throughout the r < ><4>----i <bR4>7 manufacturing ai·ea has been established as commercial manufacturing continues using these areas. For example, this matedal is located in: a. The Grade B ceilings o~CbH4> Iaseptic filling rooms~H4> I (b)(4) b. The Grade CI Ipreparation (compounding) ai·eas. (b)(4) c. The Grade Cwashing ai·ea for machine paits used to suppo1t I Imanufacturing. d. The Grade Cmate1ial weighing and dispensing ai·ea for ~H4>

Procedures designed to prevent microbiological contamination ofdmg products purp01ting to be sterile did not include adequate validation of the aseptic process.

Inadequate smoke studies is a repeat observation from the May 2025 Warning Letter. 1. For r <bR4r7 aseptic filling line lbR4> smoke studies were approved by the Quality Department that showed first air was dismpted above sterile surfaces and sterile components during interventions, such as: a. During installation ofthe r-----<bR4>~ the operator's hands dismpt the airflow to the exposed r-<bR4>-----i_ appeared to be turbulent and flowing upward during b. The airflow in the area around the'ct,><4>

Procedures designed to prevent microbiological contamination ofdmg products purp01ting to be sterile are not established.

Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions.

1. Equipment surfaces that directly contact ste1ile tb) (4) ~> <4> I equipment including the [ packa~g are not ste1ilized. ~ (b)(4) 4 X > filling line I machme contact parts ke-1eft in place between batches and cfisinfected. Failure to sterilize c1itical equipment surfaces is a repeat obse1vation from the May 2025 warning letter. 2. During cleaning of the aseptic filling line ~bX4>Jon Janua1y 13, 2026: (b)(~) a. The operator used a single wipe to clean the I I underneath the bowl, and bowl instead of getting a new wipe for each area as reqmred bySOP. The bowl was never rotated as required by the SOP to ensure all outer areas are disinfected. b. During cleaning ofthe 6H4> I, the operator failed to pull the component toward themselves to clean all areas ofthe h,><4> I c. An operator was obse1ved picking up a wipe offthe floor, throwing it away, and placing their hands into Grade A area without disinfection of their hands. d. The operators did not wipe smfaces in a unidirectional manner. e. The~>sLJ machine was not adequately cleaned, and not adequately disinfected. Due to the machine's size and height, operators were unable to reach and clean all surfaces ofthe equipment.

Written procedures are not established that describe the in-process controls and examinations to be conducted on approp1iate samples ofin-process materials ofeach batch.

1. For thect,><4> I ste1il~(bH4>1products: a. There is no 100% visual inspection process for ~! I bottles to detect visible particulates, container defects, or other quality issues at coulcl affect product safety and efficacy. b. There is no destrnctive testing to detect c1itical defects in a statistically significant number ofsamples filled into~H4> !bottles. 2. For th~ 4> I sterilQ products, destrnctive testing is used to b 4> I units for visual inspection: a. The visual inspectors were unable to consistently detect pruticles smaller than~H4>Jmicrometers (µm). No alternative approaches were used to enhance the ability to pe1fo1m the inspection an the smaller particles were eliminated from the challenge kit. b. The defect kit does not include intiinsic pa1ticles, such as b > IpruticleskH4> Ipruticles, or extiinsic pruticles such as fibers or threads for the qualification for visuaf inspectors. c. No sub-visible testing has been perfo1med as pa1t ofthe destrnctive testing.

Aseptic processing ai·eas are deficient regarding the system for monitoring environmental conditions.

There is no surface monito1ing of Grade A surfaces in the~> c41 Imachine.

Approp1iate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records ai·e instituted only by authorized personnel.

Approp1iate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records ai·e instituted only by authorized personnel. The software used to operate the ~H4> d Machine does not have individual usemame and passwords. Operators can make changes to pai·ameters like 11ling times (volume) and ~H4> I There is no audit trail to document what settings were used and any changes made.

Records ai·e not kept for the maintenance and inspection ofequipment.

Written procedures ai·e not followed for evaluations conducted at least aimually to review records associated with a representative number ofbatches, whether approved or rejected.

Your furn failed to conduct annual product reviews in a timely maimer to ensure that appropriate conective actions ai·e taken when necessaiy. XLV-PQR-RAP-0046, APR for~H4> Iremains in draft status at.the time of the inspection, approximately seven months after the review peliod ended. The draft review covers tl batches that were discai·ded during the review pe1iod. ~ out ofl(bH4> 2025 aimual product reviews were late or ai·e not yet completed for US products. *DATES OF INSPECTION l/12/2026(Mon), 1/13/2026(Tue), 1/l 4/2026(W ed), l/l 5/2026(Thu), 1/16/2026(Fri), 1/19/2026(Mon), 1/20/2026(Tue), 1/21/2026(Wed), 1/22/2026(Thu)

Procedures designed to prevent microbiological contamination ofdrug products purporting to be sterile are not fully established or followed.

Specifically, A. Aseptic techniques aimed at maintaining sterility ofsterile items and surfaces are not used at all times. 1) Sterile materials are not always handled with sterile tools. For instance, • • f, j (b)(4J,fill' • I :) i. Durmg equipment setup or1 J I ml operation (b)( 4~ a!~~ #c (b)( 4j0l/09/2025), non-sterile (b)(A~were used to remove! (b 4~covers for the ( oprr bowl and stopper chute. 4 ii. During equipment setups for (b)( ' nd vial filling operations L fl (h) (4) Batch #I (b' 14~01/09/2025 and! (b)(4~drug producfl (bH4i ial Batch # (b)( 4IO 1/10/2025), sterile scissors were placed on the non-sterile surfaces in the RABS. The scissors were subsequently used to cut open~ bags containing sterile parts such as stoppers and I (h)(4) In addition, this was observed during review ofdynamic air flow visualization study videos (VR-EV-A-0 l 0) ofthe vial filling line. 2) While reviewing approved dynamic air flow visualization study videos (VR-EV-A-150, version 4 02) ofthef (bH !filling line, the following deficiencies were noted: i. Operator was observed to block first air to the ex~sed sterileI (b)(} ith non­ ·1 r MOO h'I rfi • r (b) 4 d' • • sten e: •w I e pe onnmg: 1a ~ustme

Written procedures for production and process controls designed to assure that the drug product has the identity, strength, purity, and quality that they are purported or represented to possess are not fully established or followed.

Specifically, ' 0 A. I (b)(j are perfonned forl "•:ct~g__11roduct manufacturing. According the PPQ batch records, for example, size~ (b)(~and ~ g~(b><4J,m L, Batch size: (b)(4) C (b)(4), d . I L -~ (liJ ~ere taken 10 ......,_-,-__,,.......'an testing samp es were taKen rrom th\ ___ 1 4 Cb>< >stages of the batch productions. The current[ (b)( 4) ampling plan including tfle .,_n_u_m_b-er...ofsamples do not provide a statistically sound representation ofthe C ~ filled in the batch productions. B. Appropriate visual inspection (VI) procedures designed to assure batches otj CbH4Jproduct meet appropriate specifications and statistical quality control criteria are not established. I) 100% visual inspection of! (b}(4]~nd the acceptance testing (AQL testing) are performed in the packaging room next to packaging and labeling machinery equipment with loud background noise, and without dimmed ambient lighting. During~ filling operation for 4 L ~ atch #..._ ____, 01/14/2025, it was observed that in addition to the I CbH 4 visual inspection inspectors and..._,--_,t QL inspector,! (&)< ~roduction and QC personnel were also present in close proximity pertonning packaging, labeling, and QC sampling

Adequate procedural controls were not established to protect the electronic data acquisition and process control systems used for the manufacturing ofj (b)(4ps and DP in your manufacturing facility.

Specifically, A. Reviews ofelectronic data including audit trail information are not performed by the Quality Assurance (QA}unit for manufacturing equipment prior to the final approval ofmanufacturing_ batch

The responsibilities and procedures applicable to the Quality Unit are inadequate: A.

The Quality Unit failed to follow the deviation management SOP, 2-SMP-L (b><4}oso (5.0), by not including the recordable event RE202401 I in media fill report VR-PV-A-009 (03). B. The Alert Limit and Action Limit Management Procedure SOP, 2-SMP{ (b)(4}015 (8.0), allows alert limits to be adjusted with a CAPA that does not require a risk assessment. CAPA 2-SMP~ F,o77-R02 (4.0) was approved for loosening the requirement to investigate mold from(m:;FUE} ] (b)(4J covery to greater tha~ FUf (bH 4Jecovery in Grade C and D areas. C. The deviation management procedure, 2-SMP-~ 080 (5.0), is inadequate: 1) lt does not require a CAPA for excursions for which "the cause is clear". For example, a CAPA was not opened for recordable event RE2024011 when the particle counter exceeded the acceptance criteria inside the filling machine for vials during media fill run VR-PV-A-009 (03). 2) Abnormal events and abnormal material events are not required to be listed in validation reports. For example, I. In the! (b)(◄~drug substance batch record for preparation for! ('oH4J r~the failure ofthel (b)( 4p,achine was classified as an abnormal event and was not included in the drug substance process validatio

Laboratory controls do not include the establishment ofscientifically sound and appropriate standards designed to assure that components and in-process materials confonn to appropriate standards of identity, strength, quality, and purity: e),f)LO'fEE1S) s,:;;N,\ Tl.RE ~j -1/J, };...

There is a failure to submit a field alert report (FAR) to FDA within 3 working days of receiving information concerning bacteriological contamination in the distributed drug product.

Specifically, No FAR was submitted regarding bacteriological contamination observed in the aseptic process simulation (APS) Batch #(b) (4) !. On 25 Sep 2024, APS Batch #0C~f(4) Iwas conducted on the Kb) (4) ]filling line. On 30 Sept 2024, positive growth was observed in multiple filled units. Deviation investigation IR/DR/PD/24/049 was initiated on 30 Sep 2024 and closed on 09 Dec 2024. From 29 May 41 2024 (lasJ)(~uccessful APS) to 25 Sep 2024,r >< batches of aseptically filled[(b) (4) Jinjection USP an batches of~~ b 4 Inj~ction were manufactured on theOC~>:(4)] filling line. In addition, lbH•> batches o (b) (4) 1sterilized drug products were manufactured. These batches are currently in the U.S. market and within expiry . OBSERVATION2 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 w hether or not the batch has been already distributed. Specifically,

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

Sp ecifically, The airfl ow visualization partial studies (smoke studies) performed on the (b) (4)1 and [(b) (4) 1 filling lines show the following deficiencies. The above filling lines are used to manufacture products for the U.S. market. A. I (EL) watc~ed video ofsmoke study ofth~'[6f(4) filling line[Ilij]4) LAF for b) (4) stoppers transfer performed on 13 Nov 2023. I (EL) noted ingress of Grade Bair into the Grade A (b) (4L during transfer. I also observed the operator's deficient aseptic technique ofquick movement during transfer created disruption to the unidirectional airflow. B. I (EL) watched video of the dynamic smoke studies of th((b) (4)1 anc{6f(4) (I>~ filling line interventions performed on 04 Apr 2024. I (EL) noted the studies were 11ot conducted under dynamic conditions. Although various interventions were performed, th6(1>)(• S filling lines remained static and did not simulate the commercial manufacturing conditions.

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

Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.

Specifically, On 11 Feb 2025, during the aseptic filling of U.S. product (b) (4) njection, USP Cb) <4lmg/mL lb><•, mL), Batch #I b 4 on the b 4 filling line. The following were noted. A. Investigator Piechocki noted materials came off loose along the(D) (~) frames in th ~ BS Grade A filling room ceiling. You confirmed they are tapes used to additionally secure the (b) (4) to its frames. These tapes are approximately 2 cm in width and 135.5 cm in length. They were observed

Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions.

Specifically, 4 You conduct l b) (4) Ifor al lb> < > filling lines Grade B areas to control microbiological contamination. A ll(b) (4~11ing lines are used to manufacture drug products for the U.S. market. However, your(b) (4) efficacy study is inadequate in that the biological indicator (BI) and chemical indicator (CD locations were not justified. No risk assessment was performed to determine appropriate indicator locations. Instead of placing them in most difficult to reach places, Bis and Cis were placed in the open areas of the Grade B cleanrooms during validation.

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

Specifically, ......_____,,__ Your viable environmental monitoring (EM) results are not always reliable because the 6 4 (b) (4) plates incubation condition at 1b>(◄>(b><◄> 0c is not supported by the growth promotion test (GPT). For example, section 4.10.2 ofSOP QCB-091, entitled "Environmental Monitoring Programme fo1(b) (4) Line<b><◄> requires to incubate all E (b) (4) plates a~b><◄>(b><◄> 0c for NL111 b 4 followed by~b>(◄>(b><◄ > 0c forNLT b 4 However, during GPTthe(6 4 plates are only • ' (I>)(•) ' incubated a1!b>(◄>!b> 1•> 0c for s____ You do not have growth promotion data to demonstrate the capability o~(b) (4) media to support microorganism growth a~> 1◄><b> 1•> 0c. .

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

Specifically, A. There is no assurance that all active air sample data obtained using (b) (4) air samplers are reviewed and complete as part ofthe batch production record. Active air samples are obtained throughout the filling area within the filling line (fixed equipment) and the filling area (portable equipment) following QCB-050, "Environmental Monitoring Programme" and QCB-091, "Environmental Monitoring Programme for (b) (4) ______ Line!b>l 4>. However, upon review ofthe electronic data associated with It>><•>of the (b) (4) air samplers, 17 aborted runs were observed, including air samples collected within the (b) (4) areas and corridors. According to your microbiology personnel, these aborted runs are associated with samples which were collected, however the person collecting these samples did not visually ensure that the air sample was completed for the entire b 4 collection time, and these electronic data logs are not reviewed as part of the batch record.

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

Specifically, drug substance used for the manufacture of(D) (4) (b) (4) [njection, USP (b) (4) is tested for related compounds following method RM­ I 100478-LC-RC. According to version 00 of the method used to release drug substance batches

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

Specifically, A. Laboratory results within the LIMS system are not adequately verified to ensure that data obtained from the chromatography system are appropriately reported. For example, the total impurities related to EMPI.O f/S/ SIGNATVRE

Your multi-product manufacturing areas are not adequately controlled to prevent potential cross-contamination.

Specifically, a. There are no physical or procedural segregation controls for materials, equipment, and personnel movements between upstream and downstream manufacturing areas. b. The clean room grade (CRG) areas lack s[pecified pressure differentials between upstream and downstream manufacturing suites for ~ intermediate, and parameters for air exchange rates for the CRG manufacturing suites have not been defined. c. There are no established standard operating procedures (SOPs) for managing shared processing areas for concurrent multi-product manufacturing operations. d. During inspection, it was observed that operators in the CRG and Grade C manufacturing suites frequently left~ ---- (bH-Of , pen for extended periods with_out covers. This . d I . ~ - . f • (b)<-O~ r----(6)1:l issue occurre mu tip e times ctunng me connection o aseptic .----1LOL___ ______(b_~ ... <41on .,..,...___,,,.......,.,.--=-___,,,_...,""' (b>< 4 and ~•H 4 Additionally, opera ors were seen working in the Grade c (bH - rea without 1 masks while performing these open operations. Operators were also o served spraying f "'"ltoj •1, sanitization near ope!f ""1posing risk o(::contamination 1o l ~e .. L___,...,.___

Your QC laboratory controls used for in-process, release, and stability testing ofj (b)(4J intermediate do not include appropriate test procedures that assure conformanc_e_t.&n" appropriate standards of QUalitv and 4c,urity.

Specifically, the' -=:.,jmethod for in-process testing of Cb>< ;in.termedi,rr te (b)<"~is not adequately verified or validated (b)(4J ~ CbT(41 -w for its intended use. You reported that_ l and ~ 1/o LJut between iJ (b)(4} (b)(~ . . . ­ ofl}ests) ofl ....Jtests were mvahdated mainly ue o a1lecl system suitability criteria resulting from low% recovery of the lowest standard concentration. The lowest standard concentration for this method is also the limit of quantitation (LOQ) for the method, and is therefore, expected to have sufficient recovery. The recurring system suitability failures indicate that there is no assurance that the method is adequately validated and capable of consistently meeting system suitability criteria.

The stability program SOP "FDBT-SOP-0405 (revision 10)" is not being followed.

The SOP requires that stability testing for internal tests be initiated within the te_s_t_initiatio_o windows (b)(41 indicated in Table 2 of Section 4.4.5.5. However, review of historical ]intermediate r stability sample pulling and testing schedules from January 2024 to l'vlarcn to·2~5 showed that the following stability tests were performed outside of the testing initiation windows specified in the SOP: CEX-HPLC analysis of,Jn1 Cb><4~:~(-20°C, 24-month time-point) performed 78 days past the testing window, lot (-20°C, 24-month time-point) performed 92 days past the testing window, lo (b~~4~-20°C, 24-month time-point) performed 107 days past the testing window, lot ..(-20°C and 5"C , 6-month time-point) performed 57 days past the testin1(Wm~crow1 CbJH4l(-20°C and 5°C, 9-month time- point) performed 24 days past the testing w1naow; and-S- - PLC analysis of lot [ Cb><4J (-20°C and 5°C, 6-month time-point) performed 29 days past the testing window.

Your cleaning and sanitization program is deficient in preventing potential contamination in the controlled drug substance manufacturing areas.

Specifically, a. The SOPs (FDBT-SO~r-0_682_re\lisio~><1?; FDBT-Wl-0040, revision 12; FDBT-Wl-0347, revision 3) for Grade A; pperation and cleaning are inadequate in providing ex~licit instructions on post-use cleaning. It was observed that only the outer surfaces of 41 the~ (b)( 4:used to hold WCB vials and the cell viaar ilit sample cups were cleaned wit (b)( fwipes. However, the areas inside the (b)( 4~which had direct contact with vials and cups, were not cleaned post-use. b. Your cleaning and sanitization procedure for the manufacturing areas in th~L t"Rj facility (SOP-0322, revision 21 .0) does not require documentation and verification m the cleaning logbooks during the facility cleaning and sanitization that the treated surfaces are wetted and remain wetted for the contact time validated in the disinfectant efficacy studies. C. Your disinfectant efficacy study (Report# 22-137DET, approved 24 Jan 2023) does not adequately support the sanitization procedure for the antimicrobial and sporicidal effectiveness 'flthe..d~~~fectants and sporicidal agents on all re12resentative ma_o_ufa.cJu1~g s~urt~c~es in thE\_ jfacility. For example, materials used tor (b)( ·j 1 LJcomputer keyboa

_Envlmnmeptal monitoring (EM) of classified processing areas in your[ (b><j acility for the (b)( >jntermediate manufacturing operations is deficient.

Specif1car 1y, . a. During the routine EM monitoring of the solution preparation activity room t n March 06, 20~5, a QC analyst was obs~rved using inadeq_uate sa~pling techniqu~ er (b)( 41 plate did not make full contact with the surfaces while the viable samples were colle-cnm. b. There is no EM sampling for th~ operation.

Your fir~ faited to exercise appropriate controls for the electronic data acquisition systems used forl Cb>< 4~intermediate manufacturing.

Specifically, r (b)(4l ~m a. There is a lack of documented evidence that the,_____~-- ~ystems and the [ CbTC~system have been validated to pr~ ect onginalefectronic records an rerevar lCmetaaata (e.g., audiLtrails) J hese svste.rns are uJilized to collect and process data 4 from data loggers during theL__ Cb>< jvalidation of critical process ~ .uipm?r:,t and systems at your faciliiy,Trici'uclTng ,- -~---.---- Cb>1 4 ) L :Jin addition, audit trail review-is not performecrtor eacfiaatasetouring the valicfat1on review. During data review, only final printouts of the measurement results are reviewed, and they are not verified against the original electronic records. b. Your firm lacks an adequate program for comprehensive evaluation of the,..[---.(6,~ ~..§.tern audit trails to identify and address any aberrant trends associated with user-aborted L Cb><j sequences/injections/sample-sets events. Specifically, your firm's dataset auaiftrai1•-r-e-v,-e-w...s failed to include in-process testing_r~sults and "Trial Injections" datasets. System audit trail reviews are only performed I Cb>< 41In addition, user privilege settings in r Cb>14'allow your QC analysts to pertmm-oa1cn processing or ma

SOPs or work instructions are not followed or are inadequate.

Specifically, a. The instructions in the QC release and stability test methods are deficient to ensure conformance to appropriate standards of quality and purity. For example, 1. c::: ::.M 022-6.J Cb><1,Analysis of Cb>< 4i(revision 7). The! Cb>< 4;method is used for in-process, release, and y ing.'"there are specific sections of FDBT-TM-0226 that provide instructions (_C--0 -;,r Yanyan Cao, Ph.D., Pharmaceutical Scientist

Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions.

Specifically, J (6)(4 . A. an<\_ are being used to clean the' (b)141Gr.ade..e. ctHljng machine 1 ~ces. However, you do not have a validation study to show that theI lis effective against mold species. B. Workinstruction (WI)! (b)14l oes not contain sufficient details on how to clean 4 the (b)( filling machine surfaces. For example, the bottle bowl comes into contact with sterile bottles used to fill the sterile! (b,<, drug products. r o ;ve_ye.r the only inJ~truction written in the above WI is to "Clean the inside ofthe bottle bowl". (bH ;ctoes not have adequate cleaning details to prevent microbial contaminkhon orclrug products purporting to be sterile.

Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.

Laboratory records do not include the initials or signature ofa second person showing that the original records have been reviewed for accuracy, completeness, compliance with established standards.

Specifically, On 11/13/2024, I (EL) reviewed the! <6TT4 ~ 1l lines Grade D ~gowning room) viable (bT<4!air and surface monitoring records.[ (b,c4 p ut ofthe total! (b) ro: !ates reviewed showed maccurate colony enumerations. The discrepancy was confirmed by the QC Microbiology supervisor. Your environmental monitoring data is not subject to second-person review to make certain that all test results and associated information are appropriately reported.

The information provided by the firm does not conform to the{b)(4) ~cifically, in the H4> the(b)(4) drug substance (DS) shelflife iS(bH4> at :$(b><4> C.

However, the shelflife applied to DS Process Performance Qualification (PPQ) batches (Batch(b)(4) and post- PPQ batches (Batch(b)(4) waS(b)(4)

The(b)(4) (b)(4) integrity test procedure used for thc(b)(4) does not follow the vendor recommendations (documenC ,n versio~ or SOP CHVI-346656 v2.0 '~H4> IOperation of(b><4> and Integrity Test of(b><4> ~(4) {,'.

For example: a. (b)(4) lversio11:(b><4> indicates to.__ _ __, <6H4> for test set-up. However thelbH4> or test set-u is in(b><4> per SOP CHVI-346656 v2.0 Figure<bH4) 'he according to the guidance shown in \U)\~, the(b)(4) Manufacturing Executing System (MES) guidance for the operators. b. (bH4> 1versioij(bH4> "indicates that the(b><4> should be (bH4> ____________(b>_c4_>______, _________This step is not inc.Jnde.dj n SOP CHVI-346656 v2.0 or in th1(b)(4) ¥ES guidance for the ope~ators. c. (b)(4) version(b)(4) indicates to observe and disregarofilill 7 that occur in the(bH4> 2 (b)C4> (waiting time), and to observe the.._(b-)(4~>____] __ for:ci,>_m .-----(observation time). i. The(b)(4) lMES instructions indicate to start the timer immediately after the(b)(4) is (b)c4> ruicl.conduct the test for~ c4> 1£ohc:;er_vatio.n..time) witbou\ r entioning any . . . (MES . . ~ h (b) o wa1tmg time mstruct1on patus1

Process Parameters (PPs) are not adequately controlled within established ranges iDCb><4> DS manufacturing process.

Specifically, PP deviations occurred duringr,><4> post-PPQ Batch(b)(4) and BatchCbH4>manufacturing, including deviations for Critical Process Parameters (CPPs). In addition, Batch H4> and BatchCbH4> ad out-of-specification (OOS) and borderline results, respectively, fol1"p,><4> I assay at release. The CPP deviations observed include: a. ~_<4> ---=---c-_batcfl(b)(4) outside proven acce table range on )(4) Stage): duringCb> <4> of productiorr>(4) ,step for Batch Cb> (4) (a CPP) waS(b> <4> f chwas e PAR ofn,)(4) ~ nd NO~ ofr,><4> for:ci,>~> hCbH4>andCbH4> exceedance forCb> c4> -------=~ ;-------­ as per CHVI-626612): during(b><4> manufacturing for Batch atc%u4> _Jiad )(4) ~ Cb>~4> espectively which limit, andr)(4) halo,)(4) which exceeded the :'.SCb)(4) o ff(b)(4) limit. CbH4> fo~lbH4)___, and(bH4> are CPPs. C. (b)(4) Batch(b)C4> Excursion o:Ji(b><4> during'Cb><4> during the(b)(4) ste for Batchb><4> the (b)(4) was....r-ep_o_rt_e_d_ru_,Q(b)(4) the acceptable range iS(b)(4} Cb 4 ._____....;.-------­

Critical material used to manufacture(b)(4) is-not tracked, maintained, or replaced throughout their lifetime.

SRer.i:6r.::iJ1v._·______..., a. The(b><4> ~ grity Tester used fo~(b)(4) r------, including ther,><4> (b)(4) DSCb><4> Cb/\ 4 ) (SAP No: CbH4> installed 4 "6etweeli1£e_,_____,_____-,...,Cb>< > to avojd,..". o~the product(b)(4) entering and damaging the instrument. The(b)(4) is not tracked or maintained and is replaced only when damaged. During the FDA inspection oftheCb><4> internty_te~t execution on October 24, 2025, a'(bH4> __________..., coming from the(b)(4) through the(bH4> r~hm~ approx1mately(bH4> Impact ofthe(b><4> in the results ofthe(b)(4) ,.------ ~ntegritY. test c_aruiot be discarded. .....,. b. The(b)(4) .---- instrument used to sea\(b)(4) ____,drug substance bags does not have a unique tracking number, and is not maintained or calibrated. c. The /h)/4) used for the CbH4 >'~------1or for the_(b_> <~4>~_. 1 !b> C4> do not have a preventative mamtenance program. The product contact part ofthe (b)(4) and replacedb c4> ] however, maintenance ofthe_(b>...;.<4""'">--:-:" ~ t th is "failure-based" (they are used until they fail, and then they are replaced by a working(b)(4) The facility has a single spare(b><4> to be used as replacement for the,_~>_<4>___. ""'4' used forI!>>m a

Donors were not screened by a review of relevant medical records for risk factors of communicable disease agents and diseases.

Specifically, From June 2022 to January 2025, your firm failed to adequately screen directed donors of semen and oocytes based on your donor medical history interview titled, F-DNE-253"FDA Screening Questionnaire for Risk Factors and Conditions" revision 6 effective 6/20/2022 through revision 9 effective 1/29/25. Your questionnaire failed to screen risk factors for Creutzfeldt-Jakob Disease (CJD), a relevant communicable disease agents or diseases (RCDAD). The initial question, Question #24, asks " , but does not include time spent in the and if answered no by the donor, the questionnaire instructs the donor to skip questions #24a, b, and c, which are: x Question #24a. "

You did not establish and maintain procedures for screening of HCT/P donors.

Specifically, Your procedure titled P-AE-2025 "PROCEDURE FDA regulations" revision 8 effective 1/10/2024, does not address all steps in performing donor screening. For example: 1. The procedure does not address what RCDADs must be screened during review of a donor's relevant medical records. For example, see OBSERVATION 1 for deficient screening questionnaires. 2. The procedure does not address what clinical evidence to look for when screening a donor for RCDADs. 3. The procedure does not address making inquiries into records and other information when the circumstances indicate that follow-up information might be relevant for screening a potential cell or tissue donor.

Quality oversight is inadequate.

Specifically, a. There is a lack of a separate and independent quality assurance unit needed to perform objective review. b. Internal audits are not performed at the defined frequency according to the Quality Manual. c. No independent review of final test reports and associated test data is performed. d. An administrative staff member was identified as acting Quality Assurance Manager, and no evidence was found that this individual performs any quality assurance activities as defined by Quality Manual and confirmed per employee. e. SOP ADMIN006, How to Write a Standard Operating Procedure, does not require review and approval of any technical or QA procedures. No evidence was found of any QA review of any controlled SOPs. f. Per the Clongen Quality Manual, (b) (4) review is required to be conducted by the Laboratory Director and the Quality Assurance Manager to assess current policies, practices and procedures to determine effective changes. Clongen stated that (b) (4) review has not been performed since 2023. However, that is no evidence of any reviews being performed.

Written procedures are not established for critical laboratory tasks.

Specifically, for: a. Sample receiving and (b) (4) when receiving sample shipments from (b) (4)

Equipment is not qualified or monitored for its intended use.

Specifically, a. Technician was observed using out of calibration equipment (pipette and thermomixer) during the extraction step for mycoplasma testing on June 16, 2025. (©) @) of® pipettes on a rack were discovered to be out of calibration. b. Preventive maintenance (PM) and calibrations requirements are not established and routinely performed on critical equipment including the (b) (4) PCR System (ID#(®)(4)), (b) (4) Thermomixers# (6) (4) (b) (4) gel imaging system (ID #(6)@4)), Electropheresis (b) (4) (ID #H(b) (4), and ©) @) (ID # ®)@)), c. Qualification studies were not initially performed on the (b) (4) and (b) (4) freezers prior to use.

Quality control documentation and practices are inadequate.

Specifically, a. Test runs are not documented during performance including (b) (4) of electrophoresis gels, critical test parameter checks, and reagents lot numbers and expirations. b. Quality control of positive controls is recorded on an (b) (4) with no record of (b) (4) (b) (4)

Employee training and qualification is inadequate.

Specifically, administrative staffmember performs essential tasks such as (b) (4) with no evidence of training on updated procedures or non-existing procedures.

A quality agreement defining the roles and responsibilities of each involved party is not established.

Specifically, there is no quality agreement established with (b) (4) regarding mycoplasma release testing.

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

Specifically, I) The following deficiencies were identified during the review of the Smoke Visualization studies conducted in October 2025 for the <Redacted B4> ISO 5 Laminar Air Flow Hood (LAFH) (Equipment 10: 00167) in which sterile 2 GM Magnesium Sulfate in 5% Dextrose 50 ml Bag Injection is produced: a. Processes which occur during routine operations, such as sanitizing the Magnesium Sulfate vial stoppers and drawing 4 mL from the vial using a syringe, sanitizing each 5% Dextrose Bag Injection Port, injecting the contents of the syringe into the Dextrose bag, and placing an IV seal on each IV port injected, were not simulated during the Dynamic Smoke Study. b. During the Dynamic Smoke Study, the smoke was positioned away from the technician and the area where the technician was performing operations within the LAFH; as a result, the airflow pattern over the operations could not be visualized. C. The set-up of environmental monitoring (EM) plates and units within the LAFH were not simulated during the smoke study and the units were not turned on during the smoke study to demonstrate the air flow pattern. 2) The following deficiencies were identified during the review of the Smok

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

Specifically, The following deficiencies were identified during the facility walkthrough on 05/ 18/2026 within the <Redacted B4> ISO 5 Laminar Air Flow Hood (LAFH) (Equipment ID: 00167) which is used for producing sterile drug product 2 GM Magnesium Sulfate in 5% Dextrose 50 m L Bag Injection: 1) Scratches were observed on the HEPA filter grate, and the grate was observed to be curved inward (indented) on the left side of the ISO 5 LAFH. Additionally, similar inward curve/ indentation of the HEPA filter grate was observed in the Dynamic Smoke Study video which was conducted in Ocrober 2025; 2 GM Magnesium Sulfate in 5% Dextrose 50 mL Bag Injection Lots 74946 (BUD: 08JAN26) and 75101 (BUD: 24JAN26) were compounded in the ISO 5 LAFH on <Redacted B4> and <Redacted B4>, respectively. 2) Cracks were observed on the interior of the plexiglass side panel on the right side of the ISO 5 LAFH. Additionally, similar cracks were observed on the plexiglass in the Static Smoke Study video conducted in October 2025; 2 GM Magnesium Sulfate in 5% Dextrose 50 mL Bag Injection Lots 74946 and 7510 I were compounded in the ISO 5 LAFH on <Redacted B4> and <Redacted B4>, respectively. 3) Yellow stains th

Acceptance criteria for the sampling and testing conducted by the quality control unit is not adequate to assure that batches of drug products meet appropriate statistical quality control criteria as a condition for their approval and release.

Specifically, The firm's Quality Unit does not perform independent Acceptable Quality Limit (AQL) sampling and testing of finished sterile drug products following 100% manual visual inspection. The firm's procedure # SC-03 ·•Final Visual Inspection of Compounded Sterile Preparations (CSPs)" does not include instructions for Quality Unit AQL sampling and testing. Without independent AQL testing by the Quality Unit, there is no objective, statistically sound evaluation of whether released product is essentially free of visible defects. Specifically, Sterile Drug Product 2 GM Magnesium Sulfate in 5% Dextrose 50 mL Bag Injection Lot 74946 (Compounding Date: <Redacted B4> BUD: 08JAN2026; Batch Size: '( <Redacted B4> Units) and Lot 75101 (Compounding Date: <Redacted B4>; BUD: 24.IAN2026; Batch Size <Redacted Units) were each released following 100% visual inspection performed solely by the same compounding technician who produced the respective lots, without any independent AQL sampling or testing performed by the Quality Unit prior to release for distribution.

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, The firm's procedure# SC-03 "Final Visual Inspection of Compounded Sterile Preparations (CSPs)" does not include instructions for creation and characterization of the defects to be used, including the range of sizes to be used in, and instructions for the qualification of the Visual Inspection Qualification (defect) <Redacted B4>. Specifically, the defect <Redacted B4> designed on O5NOV2025 and used to qualify manual visual inspectors is inadequate in that the particulates contained in the defect <Redacted B4> are of unknown size. No threshold studies (e.g., probability of detection studies) have been performed to determine whether the particulates in the <Redacted B4> represent the range of defect sizes likely to be encountered in the finished sterile drug product, and whether trained personnel can reproducibly detect them. As a result, there is no scientific basis for concluding that the compounding technician, who was qualified on the <Redacted B4> on 06NOV2025, and who conducted the 100% visual inspection of Sterile Drug Product 2 GM Magnesium Sulfate in 5% Dextrose 50 mL Bag Injection Lot 74946 (Compounding Date; <Redacted B4> and Lot 7510 I (Compounding Date: <R

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, The contact times maintained during the cleaning and disinfecting of the Cleanroom Suite and the ISO 5 LAFH, used for producing sterile drug product 2 GM Magnesium Sulfate in 5% Dextrose 50 mL Bag Injection Lot 74946 (Compounding Date: <Redacted B4>) and Lot 7510 (Compounding Date: <Redacted B4> are not documented. The firm's procedure# SC-I7 '·Sterile Compounding Area Cleaning and Disinfecting" specifies a required minimum contact time of <Redacted B4> for <Redacted B4> and <Redacted B4> and a minimum of <Redacted B4> for <Redacted B4> <Redacted B4> however.the contact times are not recorded in the compounding batch records or cleaning logs and the firm 's procedure SC-17 does not require documentation of the contact time.

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

Specifically. 1) No assessment of retain samples, batch records, and laboratory testing data were conducted at the time of receipt of the below listed complaints, as required by the firms procedure# QA-IO ··customer Complaints Management" Steps 7.6.1 and 7.6.3 which states that Quality investigates the complaint to determine if the compounded product may have resulted in a Quality Non-Adverse Event, Adverse Event, or Serious Adverse Event and Quality checks retain samples, batch record, and laboratory testing data for the reported lots, respectively. a. Complaint# CR25-540 (SKU: 03 1098; Product: Holixia Solution (Minoxidil 7%/Progesterone 0.1 %; Lot# 71065): Patient Complaint Description: Getting severe migraines and causing scalp to burn/itch. b. Complaint# CR25-389 (SKU: 031098, Product: Holixia Solution, Lot# 71065): Patient Complaint Description: Patient experienced itchiness and redness on the skin/itchy scalp. c. Complaint# CR25-365 (SKU: 031098; Product: Holixia Solution (Minoxidil ?%/Progesterone 0.1 %; Lot# 71065): Patient Complaint Description: Burning scalp and she felt .. bumps" on her scalp. d. Complaint# CR25-538 (SKU: 141057; Product: Melidu Emulsion; Lot #7 1466)

Procedures designed to prevent objectionable microorganisms in drug products not required to be sterile are not established, written or followed.

Specifically, The firm's non-sterile topical drug products and <Redacted B4> Water, used in producing the non-sterile drug products, are not routinely tested for objectionable microorganisms such as Burkholderia cepacia complex (BCC) . <Redacted B4> Water is used as an ingredient in the formulation of topical drug products including, but not limited to, Clobetasol Propionate 0.05%/Niacinamide 4% Solution and Hydrocortisone 0.5%/ Hydroquinone 8%/Tretinoin 0.025% Emulsion. Additionally, the firm 's procedure# TM-47 "Microbial Analysis of <Redacted B4> Water at SKNV FL" does not require testing of the <Redacted B4> Water for BCC.

Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.

Specifically, your firm failed to ensure that the laminar airflow hoods used for the production of sterile and non-sterile drug products were maintained in a state of adequate control. During the <Redacted B4> cleanroom certification conducted on January 28, 2026, a <Redacted B4> laminar airflow hoods at your facility were found to be operating outside the acceptable airflow velocity range at the time of certification, as documented by the as-found FAIL designation in Certification Report #02647-20260128RTO1 : <Redacted B4> Your firm did not initiate an investigation or quality related event in response to these findings and did not conduct a product impact assessment for sterile and non-sterile drug products produced in these laminar airflow hoods since the previous <Redacted B4> certification in July 2025. feUe1.i,iiR~

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 has not conducted annual product reviews for any drug product in your portfolio. Your Quality Assurance Manager confirmed that no annual product reviews have been completed and that the standard operating procedure governing the conduct of annual product reviews has not been approved and remains in draft form. The following drug products have been in commercial production for more than one year without an annual product review being conducted: • Lorazepam 0.25 mg/0.125 mL Oral Solution -commercially produced since November 28, 2023 <Redacted B4> batches to date) • Lorazepam 0.5 mg/0.25 mL Oral Solution -commercially produced since November 28, 2023 <Redacted B4> batches to date) • Phenylephrine Hydrochloride Injection 0.1 mg/mL -commercially produced since January 29, 2024, <Redacted B4> batches to date) *DATES OF INSPECTION 5/27/2026 (Wed), 5/28/2026 (Thu), 5/29/2026 (Fri), 6/01/2026 (Mon), 6/02/2026 (Tue), 6/03/2026 (Wed) AMEN DMENT 1

Facilities and equipment used in the manufacture of Fibrinogen are not in a state of good repair or are in a state of uncleanliness.

Specifically, a. On June 12, 2025, paint chipping was observed in the in, Production Site ® Manufacturing Suite while was being pertormed via . b. On June 12, 2025, in Production Site ( Manufacturing Suite0) (4) dry residue was observed underneath where ine PA) we hung, c. On June 12, 2025, in Production Site @ Manufacturing Suite ©) @) rust and residue were observed on the of the Grade area. d. On June 12, 2025, in Production Site Room (Grade™cracks were observed on the floors. e. During observation of of the DS manufacturing process at Production Site — Manufacturing Suit Grade on June 12, 2025, visible residue was observed on the lid ofan The addition of |) (6)(4Y is performed via an step during Fibrinogen (Human) (BT524) DS manufacturing. f. Centrifuges used for the purification of Fibrinogen DS intermediates by (B) (4) treatment, located in Manufacturing Suite(B)4)(Grade™, showed visible spots on various surfaces. g. Additionally, documentation ofequipment cleaning in (b) (4) suite(YA) Grade is not performed.

‘The design ofthe Fibrinogen activity assay is deficient.

Specifically, the in-house Fibrinogen (Human) reference material that has not been calibrated against a current International Standard for Fibrinogen. Dates of inspection: June 12, 2025 (Thursday), June 13, 2025 (Friday), June 16, 2025 (Monday). June 17, 2025 (Tuesday), June 18, 2025 (Wednesday), June 19, 2025 (Thursday) and June 20, 2025 (Friday). ! a Mae

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

Specifically, written procedures do no include sufficient details to ensure consistent implementation and written procedures are not always followed in that: i) your procedure for good documentation practices, SOP No: QA-013-01, titled Procedure for Maintaining Good Documentation Practice, Effective January 1, 2024 states, "All documents should have the signature and date of the person who prepared the document, review of the documents and approve the document." However, during a review of your log books the following was found: a) Logbook for 2023 Stability Sample Location Chart, Register Reference No: QC-042:A11, the date and signature of the employee performing the action is not documented. b) Logbook for 2025 Entry Log Card for Sample Reconciliation, Register Reference No: QC-042, the date and signature of the employee performing the reconciliation is not documented.

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

Specifically, A) Your quality unit failed to ensure that appropriate controls are in place to isolate the technical services laboratory from ongoing construction (start date 03/02/2026) in the adjoining room. Endotoxin sample preparation and testing is ongoing during construction. Change Control Plan CCP 26-001, approved by Quality Assurance on 02/09/2026, states that construction is not expected to impact laboratory operations. (b) (4) sheeting is currently hung between the lab and construction area but is unsealed with gaps between the sheeting and laboratory walls. Additionally, on 03/24/2026 we observed construction personnel temporarily removing the (b) (4) barrier, exposing the construction area to the laboratory. Dust is present on the laboratory side of the sheeting and on the laboratory floor near the construction area. Air purifiers have been installed on laboratory benches to mitigate the impact of airborne particles during construction, use of which was not evaluated in CCP 26-001. Your Associate Director of Technical Services indicated they are unaware of the potential impact of airborne dust on sample integrity or endotoxin test results. CC 26-001 did not include an e

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

A. Your firm failed to complete Analytical Method Verification Studies for the following USP methods used to test (b) (4) : 1. Assay: (b) (4) 2. Impurities ((b) (4) ): Impurities Testing in (b) (4) (b) (4) 3. Example: (b) (4) USP (b) (4) Loté(b) (4) B. Your firm failed to complete Analytical Method Verification Studies for the following USP methods used to test (b) (4) : 1. Assay: (b) (4) 2. Impurities ((b) (4) (b) (4) , and (b) (4) ): Impurities Testing in(b) (4) 3. Example: () (4) USP (b) (4) BN#(b) (4) C. Your firm failed to complete Analytical Method Verification Studies for the following compendial methods used to test (D) (4) ((b) (4) ) 1. Assay: Chromatography <621> 2. Example: (b) (4) Tank# (b) (4), QC# (b) (4)

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

Specifically, 1. Your firm does not perform specific identity testing on each container of each shipment of each lot of(b) (4) used in the manufacture of OTC drug products, such as (b) (4) suppositories. The following lots were released without appropriate identification testing e § lots of various count sizes of (b) (4) suppositories in 2025, totaling approximately (b) (4) doses distributed 2. Your firm does not perform all required identification and compendial tests for(b) (4) . Testing for these components has been reduced despite their classification as high-risk materials. Full compendial testing is not conducted to ensure the quality, purity, strength, and suitability of these components prior to use in drug product manufacturing. The following lots were released without appropriate identification testing e § lots of various count sizes of (b) (4) suppositories in 2025, totaling approximately (b) (4) doses distributed

Equipment for adequate control over humidity and temperature is not provided when appropriate for the manufacture, processing, packing or holding of a drug product.

Specifically, During the inspection, a walkthrough of the (b) (4) stability chamber set to operate at "°C + °C /™% RH +8% RH revealed the use of an (b) (4) , unqualified device to assist with temperature control while OTC drug products were on stability. The () (4) device had not been qualified, validated, or approved for use in maintaining required stability conditions.

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

Specifically, Your firm’s written procedure titled “Annual Product Review” requires the preparation and maintenance of APRs for all OTC drug products. During the inspection, APRs for calendar years 2024 and 2025 were requested for all OTC drug products manufactured at this facility. Your Quality Unit was only able to provide one (1) APR for (b) (4) for 2024. Your firm currently manufactures over” different OTC drug products; however, APRs have not been completed for the majority of these products, indicating that APRs were not conducted in accordance with your established procedure.

Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product.

Specifically, During the inspection, the manufacturing process for (b) (4) suppositories was observed. Your firm compounded (b) (4) in a designated compounding tank, and the compounded material was held in the tank for multiple days without proceeding to the next step of production. Your Quality personnel confirmed that your firm does not have data or studies to support this hold time for compounded material in the compounding tank.

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

Specifically, your firm has not adequately qualified the DNA plasmid reference standard’ (b) (4) used in the test method TM-0059 Determination of Lentiviral Vector Titer by (b) (4) (6) (4) in Quality Control. This test method relates to the viral vector Anti-BCMA02 CAR aLVV used in manufacturing drug product ABECMA. Three testing reports speak to the structure of the DNA Plasmid (lot ®) (4)) expected to be (6) (4) bp in length but give conflicting data: 1.Report (b) (4) dated (Bb) (4) _— for (b) (4) with size of(6) (4) bp 2.BioInformatics Report dated) (DB) (4) — shows (b) (4) total size of (b) (4) bp 3.Report #RPT-2265 dated _(b) (4) shows (b) (4) plasmid with size greater than or equal to (b) (4) bp. This plasmid reference standard lot has been used in all testing of viral vector batches with TM-0059 since prior to 2021.

Your HACCP plan does not include control measures that will consistently produce a 5 log reduction in the most resistant microorganism of public health significance that is likely to occur in the juice, for a period at least as long as the shelf life of the product.

Specifically, Your (6) (4) entitled "(b) (4) (b) (4) "and dated 11/27/24 does not ensure a 5 log reduction in the pertinent microorganism for all juice products that you manufacture, throughout their shelf life. 1.) The following products are not included in the validation study: Detoxifier, Tropical Blend Juice, Aloe Vera Juice, Turmeric Juice, Peach Juice, Raspberry Lemonade, Strawberry Juice, Watermelon Beet Mint, Pear Juice, Prickly Pear Juice, Lychee Juice, Apple Cloudy, Celery Juice, Kale Juice, Spinach Juice, Kale Spinach Apple, Carrot Ginger, Carrot Beet Ginger, Carrot Apple Beet Orange, Citrus Pomegranate, Calamansi, Meyer Lemon Juice, Key Lime Juice, Lemonade Ginger Turmeric Mango, Mango Go Go Smoothie, and Strawberry Orange Mango Ginger Juice. 2.) The validation study does not address all pertinent microorganisms for products included, such as Hepatitis A Virus and Norovirus for Strawberry Lemonade and Strawberry Smoothie. 3.) The validation study did not assess pathogen recovery or growth under normal and moderate abuse conditions over product shelf life.

You are not monitoring the sanitation conditions and practices with sufficient frequency to assure conformance with current good manufacturing practice including safety of water that comes into contact with food or food contact surfaces, including water used to manufacture ice, condition and cleanliness of food contact surfaces, prevention of cross-contamination from insanitary objects and exclusion of pests.

Specifically, 1.) Apparent rust and missing pieces of metal were observed on the blade of your (6)(4) blender. In addition, apparent black grime was observed to be embedded around the inside rim of the blender lid. This blender was used in production of Cucumber Juice, lot (6) (4) . 2.) Cutting boards were observed to be heavily nicked, with two boards exhibiting black stains. Workers were observed chopping cucumbers on these cutting boards on 8/12/25 and 8/13/25. 3.) One cockroach-like insect was observed scurrying out from underneath a pallet holding cases of cucumbers on 8/12/25. One live cockroach was observed on crates being used to hold (6) (4) of cucumber juice during (6) (4) on 8/13/25. One live cockroach was observed by the door leading from your break area to the production room on 8/13/25. One dead cockroach was observed by the door leading from the hallway to the production room on both 8/13/25 and 8/20/25. And one live cockroach was observed in your office area near (6)(4)" on 8/28/25.

Your review of critical control point monitoring records does not ensure that the records are complete.

You did not fully implement the verification and recordkeeping procedures listed in your HACCP plan.

Specifically, 1.) You did not maintain an (6)(4) Log for the (6) (4) Report dated 8/14/25, for Lot ID (6) (4) (contaiming Cucumber Juice, lot (6) (4) ). 2.) You did not review your Product Temperature Monitoring Forms for the time periods 5/21/25, 6/03- 06/25, and 7/03/25. 3.) You did not review your (6) (4) Bag Inspection Logs for the time periods 6/02-04/25, 6/05- 06/25, 6/09-12/25, and 6/16-19/25. This is a repeat observation from the previous inspections conducted in March 2024 (written observation), October-November 2022 (written observation), and June 2019 (written observation).

You did not review all of your calibration records within a reasonable time after the records were made.

Specifically, You did not review your pH Calibration Logs for the time periods 6/03-05/25, 6/06/25, and 6/11-12/25. *DATES OF INSPECTION 8/12/2025(Tue), 8/13/2025(Wed), 8/20/2025(Wed), 8/28/2025(Thu), 9/03/2025(Wed), 9/04/2025(Thu), 9/08/2025(Mon)

Records fail to show test results so as to provide a complete history of the work performed.

Specifically, During review of donor test records, serum protein electrophoresis records failed to include a quantitative Total Protein result to provide a complete history of the work performed. You fail to receive quantitative results from the contract laboratory for Total Protein and instead accept the interpretive value as your result. You currently receive these results as interpretations of results that are listed as N, ABN-L, and ABN-H. Additionally, Center Medical Specialists do not review protein values that are reported. A review includes ensuring a hold is placed on the donor and 14-day medical screening is failed. Donor holds are reviewed to ensure the donor has not had (BD) (4) consecutive unacceptable results. These results are utilized in donor eligibility determination.

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

Specifically, During observation of donor arm preparation and venipuncture, I observed three collections where your

The standard operating procedure fails to include a written description of the procedures for investigating adverse donor and recipient reactions.

Specifically, During review of Donor Adverse Event Reports, donor ™""""° had a donor adverse event (DAE) on 10/12/2025, which resulted in emergency services transporting the donor to the hospital. The DAE resulted from improper set up by Phlebotomist an , which cause a centrifuge spill. The centrifuge spill resulted in a red blood cell loss for the donor. Deviation record 2711266 does not include discussion with employees involved, investigation into improper set-up, or immediate actions with the employees involved.

Written procedures have not been developed for the of post marketing adverse drug experiences.

Specifically, procedures for vendor qualification and auditing have not been followed concerning the PV vendor, initially contracted in 11/2021, with no initial qualification, annual reassessment, or contract- required audit each 2 years. ͘ ͘ ͘ ͘ ͘ ͘ ͘

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, A) Inadequate Cleaning Validation Your cleaning validation (Disinfectant Efficacy Study) does not evaluate whether your cunent cleaning agents and procedures effectively remove hazardous drug products to prevent cross -contamination or product carryover . The cleaning agent manufacturer study provided as evidence for hazardous drug removal is inadequate for the following reasons: Your firms pellet press and metal detector are used during the manufacturing process of all hazardous drug products such as Testosterone, Estradiol, and Progesterone. For example, your firm used the <Redacted B4> Tablet Press and <Redacted B4> Metal Detector during the production of Testosterone 50mg Cholesterol, Lot 02242026TN2, expiration date 02/11/2027 and Estradiol 6mg, Lot 11202025TN2 expiration date 11/20/2026. Both sterile finished drug products were approved and released for distribution. • It only evaluated Estradiol and Progesterone not all hazardous dmg products manufactlued at your facility. • It only tested <Redacted 4> surfaces, not other product contact materials such as the plastic components of your firm's metal detector. [(6) (4) I • It is not representative of your current

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

Specifically, Your firm has failed to establish hardness specifications to demonstrate that these drug products conform to appropriate quality standards. Your hardness analyses demonstrate wide ranges of intra-batch results. For example, such variability was observed in the following lots: Drug Product Lot Hardness Test Results Low (kgF) Hardness Test Results High (kgF' Qty Made Qty Distributed Testosterone 50mg Cholesterol 02242026TN2 4.4 20.9 <Redacted B4> Testosterone/ Anastrozole 10014mg 08262025TN2 5.4 13.6 Estradiol 10mg 10212025TN3 8.3 12.7 Testosterone 100mg SA 01232026TN4 4.7 15.0 Testosterone 200mg SA 01222026TN3 13.1 20.7 Progesterone 100mg 04262024TN2 1.02 2.63 Testosterone 200mg SA 03272024TN3 4.76 11.86

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

Specifically, Your procedures do not require investigation when Acceptable Quality Limit (AQL) sampling fails after 100% visual inspection. On July 10, 2025, during visual inspection of Ascorbic Acid Preservative Free Injection batch SP2500050, (batch size: <Redacted B4> units), your initial 100% visual inspection rejected 80 critical, 49 major, and 12 minor defects. Subsequent AQL sampling identified 5 major defects, exceeding your acceptance criterion of <Redacted B4> major defects, and the AQL failed. Your Quality Unit approved proceeding to <Redacted B4> visual inspection without initiating an investigation to determine why the initial 100% visual inspection failed to detect the 5 major defects found during AQL sampling, without documenting the rationale for this decision, and without evaluating whether other batches may be similarly affected. After <Redacted B4> visual inspection and tightened AQL sampling (which passed), the batch was released. Your procedure PRD07 "Visual Inspection", Revision 00, Effective Date 09/09/2025, does not require investigation of AQL failure before proceeding to <Redacted B4> re-inspection.

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

Specifically, Your firm lacks adequate controls to ensure the integrity and reliability of analytical data generated by High-Performance Liquid Chromatography (HPLC) systems used for release testing of sterile drug products.

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

Specific ally, A. Non-Viable Particle Monitoring Probe Orientation On February 12, 2026, during the production of Glutathione (Preserved), Batch SP26012, the orientation of the non-viable particle counter probe was not directed into the flow of air in the monitored location. The probe was positioned <Redacted B4> rather than in­line with the <Redacted B4> laminar airflow, preventing representative sampling of the ISO 5 environment where aseptic manipulations occur. Your firm cannot demonstrate that the orientation and placement of the probe provides a meaningful sample of the critical aseptic processing area. B. Environmental Monitoring Equipment Obstructing First-Pass Air Your firm's procedures for environmental monitoring during production operations do not ensure that monitoring equipment is positioned to avoid compromising unidirectional airflow in the ISO 5 critical zone. Specifically, your procedure MIC0l "Viable Environmental and Personnel Monitoring", Revision 00, Effective Date 10/ 17/2025, does not provide specific instructions for the placement of settle plates and non-viable particle monitoring equipment within the ISO 5 <Redacted B4> laminar airflow hoods to ensure the

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

Specifically, Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established and followed. Specifically, A Your firm has initiated approximately 46 Excursion (EXC), representing <Redacted B4> batches of product, reports for microorganisms recovered from the ISO-5 critical zone in the Laminar Flow Hoods where sterile drug products are compounded. Since December 2024 organisms recovered included Staphylococcus species (epidermidis, hominis, capitis, haemolyticus), Bacillus simplex (clausii, infantis, circulans), Corynebacterium tuberculostearicum, Microcococcus luteus, and other organisms such as Kocuria, Peribacillus, Paenibacillus, Fictibacillus, Streptomyces, Cladosporium, Sphigmonas and Penicillium citrinum. These organisms have been characterized as either spore forming, or non-spore forming organisms recovered from either gloved fingertip, sleeve monitoring, active air, and/or passive air samples. Of the approximate 46 excursions initiated affecting multiple products batches including Phenylephrine HCL 100mcg, Oxytocin, Sucinylchlorine Chloride, Fentanyl Citrate, Labetalol, Rocuronium Bromide, Hydromorphone HCL, Diltia

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 identify the root cause of particulate contamination in your drug products intended to be sterile and failed to implement effective corrective and preventive actions to prevent recurrence. These deviation investigations have been described as, Investigation Major Particulate Matter DRL Threshold Exceedance, 100% Visual Inspection Particulate Matter Threshold Exceedance, AQL Failure, and Major DRL Particulate Matter Threshold Exceedance. Since December 2024, your firm has initiated approximately 110 deviation investigations due to visual inspection failures for particulates. The majority of the deviation reports have been initiated due to contaminates observed that presents as material found on the plunger, floating particulate, or adhered to the stopper barrel. Despite this recurring pattern of particulate contamination, your firm has not

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.

Your firm's VAL-24-076-FR, Disinfectant Efficacy Study for <Redacted B4> against EM Isolates from the Connecticut Facility Located at 755 Rainbow Road, Windsor, CT 06095, Rev.1 established a <Redacted B4> dwell time when cleaning with <Redacted B4>. Your firm uses <Redacted B4> to clean and disinfect all classified areas. The following deficiencies were noted in V AL-24-076-FR executed in December 2024. i. No evaluation of other organisms other than Bacillus subtilis (spizizenii) and the mixed culture of Bacillus altitudinis/pumilus/safensis. The firm has recovered other spore forming organisms from the ISO-5 sterile compounding core including: Penicillium citrinum, Streptomyces, Cladosporium and related organisms Peribacillus and Paenibacillus.

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

Specifically, 1. Environmental and personnel monitoring within the Lin~><4> j LAF are not ap5 priately established. The aseptic connection for connecting the ~><4> Ivessel to (b)(4> vessel for L (b><4> Img/ml drug product is performed within t e LAF on ( ine(b><4> ~ was reclassified as Grade A-Air in July 2025 with bacterial alert and action limits of r> cfu/plate and (b> cfu/plate, respectively. The area is not held to Grade A classification during this critical operation with a specification of No Growth. In addition, there is no immediate personnel monitoring conducted for the individual after completing the aseptic connection. 2. The ~><4> Ion the sterile filling lines in the ~><4> blocks are 4 installed oythe operate~) (b>< > the Grade A filling area then \UJW n rom within the Grade A filling areaci,><4> .f Tne operators garment (bwJ <4> was observed to touch the G"raae A exposed portion of the ~><4> ·7These (b)(4> are not further sanitized.

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

Specifically, There has been no asee!_Lc process simulation (media fill) conducted since July 2022 for I Cb>< 4 > mg/ml intended for the US market, which requires (b><4> =:] sing Line (b)(4) reguires an aseptic connectiol1ct,><4> and is usedwfien (b)(4) cannot be (b)(4) ~erformed on tne filing line. Since March 2024, at least m]6atches of1 I (b)(4) -7 mg/ml have been shipped to the US market.

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, Eme,!9yees engaged in visual inspection of sterile finished pharmaceutical products work u:30 1(b)(4) ] however, the qualification of the employee is only performed after ~><4> of visual 1nspect1on the first time the employee is qualified to perform visual inspection and is not performed again at subsequent requalifications. Of the (b)(4) employees qualified for visual inspection, ~><4> , ere first qualified in ~><4> Jwere first qualified irl(b~-;-i an~(b><4>l were first qualified in(b><4> with the remainder first qualified more recently, and none were challenged after ~><4> since their first qualification.

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, Investigations into issues requiring the filing of Field Alert Reports are not always complete. For example, 1. Investigation MC-EP1 -24-0107 was opened on 06/06/2024 due to a consumer complaint of an 18 mm glass t ece found in a dispensed vial of~><4> ii lnjection, USP(b)(4) mg per (b)(4) ml batch ~(b)(4) I The investigation could not fina he source of thk glass; however the roo cause was attributed to vials breaking in the ~><4> ] and leaving glass in intact vials. Corrective actions to the investIgat1on included adding new preventative maintenance to the ~><4> I 4 r Cbx >7 , adding a review of(b)(4) Irejected vials, and adaing a new visual inspection challenge vial for larger glass pieces, and requalification of the visual inspection employees; however, there is no discussion of whether or not the glass vials used for the product are still acceptable or why the visual inspection was unable to see the glass in the time and conditions of the visual inspection operations, which were not changed. 2. Investigation MC-EP1 -24-0197 was opened on 10/30/2024 due to a consumer complaint of a 15 mm glass piece found in a dispensed vial of~><4> IInjection,

Not all quarterly periodic adverse drug experience reports have been submitted within 30 days of the close of the quarter.

Specifically, quarterly Periodic Adverse Drug Experience Reports (PADERS) for Fenoprofen (ANDA 215548) were not submitted. These PADERS should have been reported on a quarterly basis since the ANDA approval date on 5/16/2023. This resulted in 10 quarterly reports that were not submitted.

Not all annual periodic adverse drug experience reports have been submitted within 60 days of the anniversary date of the approval of the application.

Specifically, Ketoprofen (ANDA 074014) Periodic Adverse Drug Experience Report (PADER) e 2023: PADER was due on 3/30/2023 and was submitted on 6/20/2023.

An annual report was not submitted within 60 days of the anniversary date of U.S.

approval of the application to the FDA division responsible for reviewing the application.

Written procedures have not been developed for the reporting to FDA of post marketing adverse drug experiences.

Specifically, your firm has not developed written procedures for the reporting of postmarketing adverse drug experiences to FDA. For example, standard operating procedure, 'SOP No. QLT-001-0, Handling Customer Complaints and Inquiries,’ Section 4.0, describes how it is the responsibility of the Chief Scientific Officer or regulatory agent designee to file 15-Day Alert and Periodic ADE Reports. However, the SOP does not describe the procedure for filing the Postmarketing Adverse Drug Experience Reports or Annual Reports with the FDA.