Global Regulatory Monitor
Regulatory News, Week 4 · 2026/9

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

Specifically, Media Fills A) Your facility failed to follow written procedure S601002, entitled "Validation of Aseptic Processes by Simulation (Media Fill)" version 12 dated 12/02/2025 that requires you to revalidate the media fill process with <Redacted B4> runs if you obtain a turbid unit. On 06/16/2025, a media fill out of specification (OOS) occurred for lot <Redacted B4> during dropper bottle operations recovering one (1) turbid unit. Your response to this OOS was limited to decertifying the individual suspected of causing the contamination. You did not assess the aseptic integrity of the manufacturing process itself or evaluate its impact on the products you manufacture. B) Your media fill process is deficient as you have not ensured interventions required by the protocol are comprehensive and are simulated by all operators. Additionally, you use <Redacted B4> vials to simulate your <Redacted B4> vialing process. You have not evaluated whether turbidity can be adequately detected in these vials. These vials are used to package drug products Phenylephrine/Lidocaine 15mg/10mg/ml (1.5%/1%) 1ml, Moxifloxacin HCL lmg/ml 1ml, and Moxifloxacin HCL Smg/mL 1ml. EM PLOYEE(S)

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

Specifically, your firm has not established adequate procedures and controls for the maintenance, certification, and qualification of HEPA filters, laminar air flow hoods (LAFH), biological safety cabinets (BSC), and cleanroom HVAC systems used for sterile drug production. HVAC failures have recurred without effective corrective action and oversight by the quality unit. For example, A) Your firm has not performed installation and operational qualification (10/OQ) for the HVAC systems and HEPA filtered air supply in the hazardous and non-hazardous ISO 7 and 8 cleanrooms, as confirmed by you, the CEO. Additionally, your firm has not established a written procedure governing routine qualification of your facility used in production of sterile drug products. B) According to your Quality Manager, cleanroom, LAFH, and BSC qualification acceptance criteria were not formally established between your firm and your contractor. Your Quality Manager stated test and acceptance criteria are based on industry standards but could not produce documentation of the criteria communicated to your contractor or the basis for their application. C) Your firm's quality unit has failed to thoroughly review

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 failures and adverse circumstances lack the depth necessary to adequately determine root cause. A review of several investigations revealed either unsubstantiated conclusions or a failure to identify root cause, particularly in cases involving repeated occurrences. Examples of these occurrences include but are not limited to: A) DEV2025047, initiated on 07/02/2025 in response to a turbid media fill unit from lot <Redacted B4> identified "operator error" as the root cause without evaluating potential impacts of other process inputs such as gowning, material sterility and handling, and environmental controls. Additionally, the root cause was attributed to an individual based on speculation, without an established process for tracing the timing of when units were filled/handled. EM PLOYEE(S)

Records of the inspections of automatic, mechanical or electronic equipment, including computers or related systems are not maintained.

Specifically, A) During post-use <Redacted B4> of the sterilizing <Redacted B4> used for prednisolone sodium phosphate 1% / moxifloxacin HCI 0.5% / bromfenac 0.09% PF, Lot PMB12152SCH BUD 12/15/2026, two (2) consecutive tests resulted in the error message " Error: <Redacted B4> Not Obtainable"; neither were recorded in the batch record, subjected to <Redacted B4> <Redacted B4> operations review, or reviewed by your quality unit. EM PLOYEE(S)

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

Specifically, you have not established a procedure to ensure critical data is reviewed and verified by a second person prior to batch release. For example, A) Data generated from environmental monitoring (EM) plates post incubation are read by a <Redacted B4> <Readcted B4> and are not subject to a <Redacted B4> review. Observations interpreted from the original data (EM plates) are recorded on a form that is ultimately reviewed by the quality unit. Your quality unit has no process for reviewing the original data generated from the EM plates for accuracy. B) <Redacted B4> conducted by Pharmacists are not subject to <Redacted B4> review prior to evaluation by the quality unit. According to your written procedure S403400, titled "Use and Maintenance of <Redacted B4>" version 3 dated 09/12/2025, <Redacted B4> electronic signatures are required to document and verify the performance for each <Redacted B4> test performed using the <Redacted B4> instrument. Your Operations Manager/Pharmacist stated that Pharmacists are exempt from the <Redacted B4> review requirement when independently performing <Redacted B4> which account for approximately "90% to 99%" of all non-hazardous <Redacted B4>

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

Specifically, Visual Inspection Operations You have not ensured that operators conducting 100% <Redacted B4> visual inspection are capable of identifying all defined visible defects across your sterile drug product containers, including vials, syringes, and eye drop containers. This is evidenced by: A) During the walk-through of your facility on 04/28/2026, we identified what appears to be bubbles in the plunger threads of syringe <Redacted B4> when reviewing the units used to qualify your visual inspection operators. Upon inquiry with your visual inspection operators, it was determined that this occurrence had neither been identified nor recognized as a potential defect type for the syringe product manufactured at your facility. The product manufactured in the syringe is Mitomycin lmg/ml 40ml. Syringe products, when distributed, are shipped via <Redacted B4>, which may involve transport. EM PLOYEE(S)

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

Specifically, A) Your finished product testing used to release finished drug products for commercial distribution and perform stability testing does not include an evaluation of impurities and degradants. B) You do not have a scientific rationale for not performing identity testing for glycerin and propylene glycol, which includes evaluating acceptable levels of diethylene glycol and ethylene glycol. These components used in part for the manufacture of sterile drug products. *DATES OF INSPECTION 4/20/2026 (Mon), 4/21/2026 (Tue), 4/22/2026 (Wed), 4/23/2026 (Thu), 4/24/2026 (Fri), 4/27/2026 (Mon), 4/28/2026 (Tue), 4/29/2026 (Wed), 4/30/2026 (Thu), 5/01/2026 (Fri), 6/01/2026 (Mon) Michael Z Weigman .. ... Si9"ed"By MICHAEL Z. WEIGMAN -S X Date Signed: 06-01·2026 16:08:06 _

There is a lack of HEPA-filtered air and an inadequate HEPA filter coverage or airflow over the critical area to which sterile drug product is exposed.

Specifically, on <Redacted B4> after the manufacture of tirzepatide for injection 26mg/ml lot 0805202 <Redacted B4> and tirzepatide/cyanocobalamin for injection 26 mg/2mg per ml lot 08052026 <Redacted B4>, the <Redacted B4> laminar flow hood (ISO-5) was operating with a pressure gauge reading of zero, indicating a failure to maintain the positive pressure required to protect the critical aseptic processing area from the influx of lesser quality air. You failed to use an appropriate anti-microbial preservative to prevent microbial proliferation within containers of multi-dose sterile drugs. Specifically, <Redacted B4> bulk stock solutions of drug products, such as tirzepatide, are stored in unclassified areas and repeatedly introduced into the ISO-5 environment over a <Redacted B4> period to draw up patient-specific syringes. This workflow repeatedly exposes the bulk container closure system to unclassified air during storage and introducing contamination risks with each re-entry. You are using <Redacted B4>. This can only inhibit bacterial proliferation; it is not bactericidal and does not provide protection against mold contamination. EIM'LOYEE(S)

The Cleanroom areas contain dust-collecting overhangs without adequate and frequent cleaning.

Specifically, on 08/05/2026, visible dust was observed on the inside of the clean room door window pane adjacent to the <Redacted B4> ISO-5 <Redacted B4> laminar flow hood in the non-hazardous compounding cleanroom <Redacted B4> which is used to produce sterile non-hazardous drug products. Throughout the cleanroom suites, doors and viewing windows feature decorative molding with ridges and ledges. These surfaces are not smooth, or easily cleanable, contributing to particulate accumulation and potential microbial contamination in close proximity to production activities for drug product intended to be sterile. Additionally, wall insulation was exposed and open to the mezzanine and warehouse area. This insulation was on the exterior of the generator room, the exterior of the ante room hallway, and the exterior of the hazardous compounding room <Redacted B4>. The mezzanine and stairs leading to the mezzanine were composed of particle generating wood particle board. In some locations, on the mezzanine, the air ducts were not connected to an exterior venting system.

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

Specifically, on <Redacted B4> after the manufacture of tirzepatide for injection 26 mg/ml lot 08052026 <Redacted B4> and bulk tirzepatide/cyanocobalamin for injection 26 mg/ 2mg per ml lot 08052026 <Redacted B4> we observed <Redacted B4> that the <Redacted B4> was not performed since the gauge used to test the <Redacted B4> appeared to be out of calibration and stuck on the pressure reading of approximately 18 PSI. This resulted in the following: EIM'LOYEE(S)

Your firm released drug product in which the strength differs from, or its purity or quality falls below, that which it purports or is represented to possess.

Specifically, the bulk tirzepatide/cyanocobalamin for injection 26 mg/2 mg per ml lot 08052026 <Redacted B4> was reprocessed when the <Redacted B4> was not performed due to a pressure gauge malfunction. This reprocessing combined the contents of <Redacted B4> approximately <Redacted B4> bulk drug vials which were then <Redacted B4> and tested for endotoxin and sterility. This reprocessing was performed on <Redacted B4> and the beyond use date assigned was 9/19/2026.

Smoke studies were inadequately performed under dynamic conditions.

Specifically, the smoke studies taken on 1/27/2025 in your ISO-5 <Redacted B4> laminar flow hoods and bio safety cabinets did not fully demonstrate laminar flow. These smoke study videos were 4 to 18 sec onds long and reco rde d by <Redac ted B4>. The video does not sh ow the air flow ov er the critical s teril e drug product preparation areas a nd the air flow patterns for hoods that are located acros s from each other. Compo undin g room <Redacte d B4> conta ins <R edacted B4 > ISO 5 b iosafety ca binets posit ioned f acing each other, approximately 2-3 feet apart. One hood is designated for nuclear blood tagging, and the other is used for the production of testosterone cypionate injectable produ ct intend ed to be sterile. No smoke study has been conducted to demonstrate that the airflow from one hood does not interfere with the airflow of the other. The smoke study videos also did not include the most dynamic conditions of use such as <Redacted B4>. EIM'LOYEE(S)

The facility is designed and/or operated in a way that permits poor flow of personnel or materials.

The warehouse / material receiving and product shipping area was found to have the following deficiencies: • Open insulation and unfinished construction was observed in the warehouse on the wall between the cleanroom and warehouse. • A recycling room at the back of the main warehouse / material receiving and shipping room is used for cleaning and storing the lead containers (pigs) used for shipping the radiopharmaceutical patient doses (syringes). In this recycle room, we observed that the firm is storing lead shipping containers (pigs) and radioactive waste such as Technetium Tc99m, Gallium Ga68 Netspot labeled containers, and Iodine 1-123 capsules. The firm is disassembling <Redacted B4> radioactive generators used for production of Technetium Tc99m. Plastic containers, lead, metal and residue from these items was observed in this recycle room. Dead roach(es), dust and debris was also observed in this recycle room. • The firm lacks controls to prevent cross contamination of lead, lead particles, and other debris from the recycle room through the rest of the facility. • A door connects the warehouse / material receiving and shipping room directly to the non­sterile compounding pro

Hazardous drugs and Highly potent drugs were produced without providing adequate containment, segregation, and/or cleaning ofwork surfaces, utensils, and/or personnel to prevent cross-contamination.

A. Specifically, testosterone compounding (a highly potent hormone), chemotherapy reconstitution (hazardous drugs), and blood radiolabeling (biohazardous material) are all performed within the same cleanroom <Redacted B4> using <Redacted B4> hoods in close proximity. There is no physical separation between the biohazardous blood handling area and the areas where non-blood products are handled. Furthermore, a shared supply table was observed containing materials for both testosterone compounding and blood radio labeling activities, demonstrating inadequate dedication and segregation ofequipment based on risk. Each ofthese high-risk activities requires fundamentally different decontamination approaches­ blood-borne pathogen decontamination, hazardous drug deactivation, and hormonal drug decontamination, respectively. The firm has not demonstrated through documented procedures or supporting evidence that the shared room, work surfaces, and equipment are adequately cleaned and decontaminated when transitioning between these activities. The performance of highly potent, hazardous, and biohazardous operations in the same unsegregated space, without demonstrated decontamination controls,

Lack of and Inadequate routine environmental monitoring in the ISO 5 area and classified areas.

Your staff stated they perform <Redacted B4> surface sampling within the ISO 5 and ISO 7 area after cleaning and disinfection. Sampling after cleaning does not accurately represent your production environment. Additionally, your staff also stated and demonstrated that when <Redacted B4> plates are unavailable, the firm's procedure is to use <Redacted B4>, <Redacted B4> on a surface, and then <Redacted B4> that <Redacted B4> onto an <Redacted B4> plate as EM surface sampling. A <Redacted B4> alone will not efficiently lift or release microorganism from a <Redacted B4> surface on to an <Redacted B4> plate compared to a pre-saturated swab. This method also does not include the use of neutralizing buffer which is necessary to neutralize residual disinfectants. This calls into question the validity of your test results.

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

Vermin or other animals or evidence of their presence was observed in the areas adjacent to production areas.

Specifically, on 08/05/2026, dead roaches were observed in the recycling room located at the back of the main warehouse, which is adjacent to areas with direct access to the compounding rooms. We observed each day of this inspection that bird feces were located on the ground outside your facility front door which could be tracked into your front office area and on to other areas within the facility. *DATES OF INSPECTION 8/05/2026 (Wed), 8/06/2026 (Thu), 8/07/2026 (Fri), 8/10/2026 (Mon), 8/11/2026 (Tue), 8/l 2/2026 (Wed), 8/13/2026 (Thu), 8/14/2026 (Fri), 8/18/2026 (Tue) Digitally signed by Roger F. Zabinski -S Date: 2026.08.18 14:50:55 -04'00' Roger F. Zabinski-S National Expert/CSO

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

Specifically, Your firm's visual inspection qualification procedure for sterile injectable drug products compounded and packaged in syringes is inadequate to ensure that visual inspectors are appropriately qualified to detect defects. A. The visual inspection qualification process does not require operators to distinguish between critical and major defects and the acceptance criteria to pass qualification is <Redacted B4> of defective units identified, regardless of defect severity. For example, the current qualification <Redacted B4> for <Redacted B4> syringes contains <Redacted B4> defects, of which <Redacted B4> are critical defects and <Redacted B4> are major defects. During qualification, operators are not required to document the specific defect type identified, and qualification proctors determine only whether the rejected units contained an actual defect. Thus, operators may fail to identify up to <Redacted B4> critical defects and still be qualified for visual inspection. B. A single visual inspection challenge <Redacted B4> is maintained for both training and qualification purposes. The challenge <Redacted B4> used to qualify visual inspectors for products compounded and

Batch production and control records do not include in-process results for each batch of drug product produced.

Specifically, Actual light intensity values measured prior to starting visual inspection are not recorded in the production batch records; instead, the records document only whether the established light intensity acceptance criteria was met using a "Yes/No" check box. For example, for Succinylcholine Chloride 20 mg/mL, 10 mL in 10 mL syringe, Injection Batch 62116169A (batch size <Redacted B4> syringes, manufactured on <Redacted B4>, BUD 10/30/2026), light intensity was measured during visual inspection, however, the batch record only documented whether the light intensity met the established acceptance criteria.

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

Specifically, Media fills or aseptic process simulations performed do not closely simulate actual production conditions or represent all syringe configurations. In addition, operators were not qualified prior to the introduction of new gowning components to ensure that the gowning was donned appropriately. A. Your firm's media fill program does not include worst-case conditions for all syringe sizes used in sterile compounding operations. No media fill has been performed for the <Redacted B4> syringe s i ze <Reda cted B4> since 2024. Approximately, <Redacted B4> batches in <R edacted B4> syringes have bee n comp ounded a nd rel ease d since O ctober 2025. For e xample, Sodiu m Ch lor ide 9 mg/ mL, <Redac ted B4> in <Reda cted B4> s yringes , Inj ection Batch 621 6915 2A (batch si ze < Redacted B4> syr inges, BU D 12/08/2026) was compounded on <Redacted B4> B. Your firm's media fill program does not adequately simulate actual aseptic production conditions. During media fills, operator fatigue, prolonged aseptic technique, and extended exposure time within the cleanroom environment are not being evaluated or challenged. Operators fill between <Redacted B4> units during a media fill,

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

Specifically, • <Redacted B4> Sterilization Performed in an ISO 8 Classified Room Batch records collected during the inspection confirm that <Redacted B4> sterilization was performed in Compounding Room <Redacted B4> which is classified as ISO 8. Specifically: Batch production records for two lots of Fentanyl Citrate/Bupivacaine HCl combination products, Lot 1019-01-2608-01 (Fentanyl Citrate 2mcg[base]/mL + Bupivacaine HCl 0.125% in <Redacted B4> added to l00mL 0.9% NaCl Bag; Master Production Batch Record No. GMP-PDT Methods-0218, Revision 01, Effective Date: July 9, 2026) and Lot 1081 -01-2608-01 (Fentanyl Citrate 2mcg[base ]/mL + Bupivacaine HCl 0.1 % in SWFI added to 100mL 0.9% NaCl Bag; Master Production Batch Record No. GMP-PDT Methods-0239, Revision 01, Effective Date: July 15 2026) -document that <Redacted B4> of the bulk drug solution was performed in an ISO 8 <Redacted B4> storage room" (Compounding Room <Redacted B4>) Specifically, in both records, Step 1.2 instructs operators to sanitize materials for transfer to this room <Redacted B4> Storage room/Compounding Room ,x. Step 1.5 identifies <Redacted B4> Storage room/Compounding Room 4as the designated area for these ope

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, Annual product review (APR) records for six drug product families -Fentanyl Citrate, Fentanyl Citrate + Bupivacaine HCl, Fentanyl Citrate + Ropivacaine HCl, Hydromorphone HCl, Morphine HCl, and Ropivacaine HCl, covering review period 2024-2025 -contain multiple numerical inconsistencies, cross-product data errors, and documentation inaccuracies. When presented with these findings during the inspection, firm management confirmed that the errors were mistakes and that connected records had not been issued prior to the inspection.

Dmg product production and control records, are not reviewed by the quality control unit to dete1mine compliance with all established, approved written procedures before a batch is released or distributed.

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

Specifically, A. Your cleanroom certification conducted on June 29, 2026, and June 30, 2026, shows that HEPA Filter <Redacted B4> in Production Room <Redacted B4> (ISO 7 ) did not pass airflow and <Redacted B4> as the report states the result as N/A and notes "HEPA Filter 8 in need of motor replacement." Your firm produced <Redacted B4> batches of drug products in Production Room <Redacted B4> between June 30, 2026, and August 4, 2026, <Redacted B4> of which have been distributed. No investigation or CAPA has been opened to assess the impact of this specific HEPA Filter on your operations.

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

Specifically, A. Your firm qualifies visual inspectors and AQL inspectors on <Redacted B4> basis. The following deficiencies in inspector qualification were identified during the inspection: 1. Following the start of operations at your new facility on February 2, 2026, your firm did not perform requalification of visual inspectors or AQL inspectors for the new facility. Instead, your firm continued to use qualifications performed at your previous facility. No assessment or justification for carrying over previous facility qualifications to the new facility was identified during the inspection. Visual inspection qualification is specific to the environment and equipment under which it is performed and qualifications conducted at a previous facility cannot be assumed to remain valid under the different conditions of a new facility.

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

Specifically, Smoke studies conducted on December 31, 2025, did not adequately reflect observed production operations. On August 5, 2026, video recordings of the production of Hydromorphone HCL 20mg/100mL CADDS lot #20260720HYD-1 , EXP November 17, 2026, completed on <Redacted B4>, were reviewed. The following discrepancies were observed in the smoke study videos: 1. The batch video, during production, showed <Redacted B4> operators performing individual tasks in each ISO 5 Laminar Airflow Hood (LAFH). The smoke studies only demonstrated one operator individually performing one task in each video. 2. The smoke study for the CADDs products shows the CADDs lined up with about 2 -3 inches of space between the CADD and the back wall of the <Redacted B4> airflow LAFH. During the batch video the CADDs were observed to be placed directly in front of the back wall with no gap. The smoke study did not evaluate this product placement configuration and therefore does not demonstrate that unidirectional airflow adequately protects the critical compounding area under actual production conditions. Additionally, during production, CADDs were observed blocking first air for components placed behin

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

Specifically, On August 5, 2026, video recordings of the production of Hydromorphone HCL 20mg/100mL CADDS lot #20260720HYD-l, EXP November 17, 2026, completed <Redacted B4> were reviewed. During this video review the following was observed: 1. Your production operators were observed placing the settle plates in the comers of the LAFHs before the start of the batch. Your SOP-0015 Environmental Monitoring (EM) Program: 503B Cleanroom, states placement should be", <Redacted B4> from the back/HEPA filter." 2. Your firm does not document the time post production E M samples are taken. *DATES OF INSPECTION

Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination. 2. Your media fills were not performed under the most challenging or stressful conditions. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility. Furthermore, the manufacture of the ineligible drug products is subject to FDA’s CGMP regulations, Title 21, Code of Federal Regulations (CFR), parts 210 and 211. The FDA investigators observed significant CGMP violations at your facility, causing the ineligible drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act. The violations included, for example: 1. Your firm failed to establish an adequate system for maintaining equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).

Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

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 an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).

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 have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. Your firm also failed to establish and follow an adequate written stability testing program that included reliable, meaningful, and specific test methods for assessing the stability characteristics of these drug products (21 CFR 211.165(a) and 211.166(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 failed to store drug products under appropriate conditions of temperature, humidity, and light so that the identity, strength, quality, and purity are not affected (21 CFR 211.142(b)).