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2026년 10월 1주차 규제뉴스

Personnel performed aseptic manipulations with exposed hair or skin.

Specifically, on August 24, 2026, while filling/stoppering lot #SMN-082426-5/2-5 of Semaglutide/Niacinamide 5mg/2mg/1 ml, we observed one of the operators working in the ISO 5 laminar flow hood with exposed skin on her forehead. The operator was observed entering the ISO 5 LFH, leaning over the bag of sterilized stoppers within the ISO 5 LFH, and placing stoppers on the recently filled vials.

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

Specifically, from July 10, 2026 to August 21 , 2026, your system for measuring pressure differential in the cleanrooms indicates negative pressure between the ISO 7 Buffer Room where the ISO 5 Laminar Flow Hoods are located and the ISO 8 Ante Room. The specification is <Redacted B4> w.c. and every data point documented in this time period was below 0.00" w.c. Your firm has made at least <Redacted B4> lots of various drug products in this time period. All have been released.

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

--~------ Specifically, your firm is not conducting <Redacted B4> testing <Redacted B4> appropriately as recommended by the <Redacted B4> manufacturer. Your firm has not identified an appropriate <Redacted B4> agent and you do not <Redacted B4> the <Redacted B4> before testing. <Redacted B4>, you attach <Redacted B4> to one end of the <Redacted B4> and attach the other end of the <Redacted B4> to a <Redacted B4>. You then <Redacted B4> the <Redacted B4> in <Redacted B4> of <Redacted B4> from the <Redacted B4> through the <Redacted B4> and look for <Redacted B4>. On August 24, 2026, we watched <Redacted B4> testing of the <Redacted B4> used in the preparation of lot #SMN-082426-5/2-5 of Semaglutide/Niacinamide 5mg/2mg/1 ml performed in this manner.

Personnel were observed manually contacting the inner surface of a sterile container or closure and manually touching a sterile product contact surface.

Specifically, on August 24, 2026, we watched the filling and stoppering of lot #SMN-082426-5/2-5 of Semaglutide/Niacinamide 5mg/2mg/1ml. Your practice is to place the sterile stoppers onto the filled vials using <Redacted B4> and then pressing down on the stoppers with your <Redacted B4> to push the stopper into the vial.

Microbial contamination was present in the ISO 5 area.

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

Specifically, technicians enter the ISO 8 cleanroom area via a door from the unclassified <Redacted B4> area. Gowning occurs in the ISO 8 area, including washing of hands, on the "clean" side of the demarcation line. There is no designated room or area for gowning. Employees who are gowned and not gowned can interact in the same space while gowning. After formulation, those employees will then enter the ISO 7 cleanroom and work in the ISO 5 hood preparing sterile drug products without changing their garb except for their sterile gloves.

Sterile drugs were exposed to lower than ISO 5 quality air.

Specifically, on August 24, 2026, we watched the filling and stoppering of lot #SMN-082426-5/2-5 of Semaglutide/Niacinamide 5mg/2mg/1ml. Your practice is to place the sterile stoppers onto the filled vials using <Redacted B4> and then pressing down on the stoppers with your <Redacted B4> to push the stopper into the vial. You then <Redacted B4> of the vials with <Redacted B4> the <Redacted B4> and take them out of the cleanroom. They may be stored overnight in the <Redacted B4> <Redacted B4> of the vials, which is the final step to finish the closing of the vials, occurs in the unclassified area of the <Redacted B4>.

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

Specifically, typical batch sizes for Semaglutide/Niacinamide and Tirzepatide/Niacinamide drug products are <Redacted B4> vials. Vial sizes can range from 1ml to 5ml for GLP1 products and up to 10ml for other drug products. Production includes <Redacted B4> the drug product into a sterile <Redacted B4> filling vials from the <Redacted B4> of <Redacted B4> drug product using a <Redacted B4>, and then manually placing stoppers on the vials. During a media fill, per your Quality Assurance/Compliance Pharmacy Technician, your firm fills <Redacted B4> vials. Your firm takes prepared media from a vial, draws it into a <Redacted B4> for <Redacted B4>, and then fills the vials using the <Redacted B4>. 1. Your firm also does not document the number of vials filled, incubated and read in the paperwork for the media fills.

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

Specifically, your firm is using active pharmaceutical ingredients and excipients that are not always USP/NF grade or are non-pharmaceutical grade. For example, a) The Certificate of Analysis (CoA) for Lot # <Redacted B4> of Methylcobalamin states "For R&D only". Your firm has made approximately <Redacted B4> lots of Methylcobalamin 5mg/ml using lot# <Redacted B4> for <Redacted B4>. b) The CoA for lot <Redacted B4> of Tirzepatide states it is for "R&D only". Your firm has made approximately <Redacted B4> (lots of Tirzepatide/Niacinamide 10/2 mg/ml and <Redacted B4> lots of Tirzepatide/Niacinamide 20/2 mg/ml using lot <Redacted B4> of Tirzepatide.

Contamination was observed in your areas adjacent to production areas.

Specifically, a ceiling vent just outside the cleanroom has water stains and what appears to be mold. On August 24, 2026, the vent was dripping condensate near the area where items to be taken into the cleanroom were wiped down for use in making lot #SMN-082426-5/2-5 of Semaglutide/Niacinamide 5mg/2mg/1 ml.

Use of cleaning and disinfecting agents that may leave residues or not adequately rinsing such agents from containers, closures, or equipment that come into direct contact with drug products.

Specifically, your firm uses <Redacted B4> and tap water to wash equipment used to make sterile drug products, including glass beakers, stir bars, and graduated cylinders. Your firm rinses the equipment with <Redacted B4> sterile water and then wipes the beakers and stir bars with <Redacted B4>. There is no wiping down of the inside of the graduated cylinders with <Redacted B4>. The graduated cylinders are used to measure out liquids such as the sterile water used during the production of sterile drug products. On August 24, 2026, we watched the cleaning of equipment to be used in the making of lot #SMN-082426-5/2-5 of Semaglutide/Niacinamide 5mg/2mg/1 ml, using this process.

Sterile products were exposed to non-sterile or non-depyrogenated supplies.

Specifically, your firm does not sterilize/depyrogenate the glass beakers, <Redacted B4> graduated cylinders, and stir bars used to make sterile drug products. On August 24, 2026, we watched the preparation of lot #SMN-082426-5/2-5 of Semaglutide/Niacinamide 5mg/2mg/1 ml. The glass beakers, <Redacted B4> graduated cylinders and stir bars were not sterilized/depyrogenated before use.

Biological indicators were not used to verify the adequacy of the sterilization cycle.

Specifically, your firm has not validated nor do you use a biological indicator (Bl) when <Redacted B4> the <Redacted B4> and <Redacted B4> used in the preparation of sterile drug products. The <Redacted B4> are used to place sterile stoppers onto the filled vials. <Redacted B4> are used to <Redacted B4> the <Redacted B4> of sterile water used in the formulation of sterile drug products.

Your firm is not storing active pharmaceutical ingredients (API) per the labeled storage conditions.

All APls are stored in a <Redacted B4> refrigerator. Examples of APls used in the production of sterile drug products that are not stored according to the labeled storage conditions include the following. Sterile drug products made with these APls have been released and distributed. a) The CoA for lot <Redacted B4> of Semaglutide API states to store at <Redacted B4>. Your firm has made at least <Redacted B4> lots of Semaglutide/Niacinamide 2.5/2 mg/ml and <Redacted B4> lots of Semaglutide/Niacinamide 5/2 mg/ml using lot # <Redacted B4> b) The CoA for lot # <Redacted B4> of Tirzepatide API states to store at <Redacted B4>. Your firm has made approximately <Redacted B4> lots of Tirzepatide/Niacinamide 10/2 mg/ml: and <Redacted B4> lots of Tirzepatide/Niacinamide 20/2 mg/ml using lot <Redacted B4> of Tirzepatide. c) The CoA for lot# <Redacted B4> of Tirzepatide API states to store at <Redacted B4> d) The CoA for lot# <Redacted B4> of Sermorelin API states to store at <Redacted B4> e) The CoA for lot # <Redacted B4> of Nicotinamide Adenine Dinucleotide+ (NAO+) states to store in <Redacted B4>. Your firm has made at least <Redacted B4> of Nicotinamide Adenine Dinucleotide+ 100 mg/ml usi

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

Specifically, (A) The firm's environmental monitoring procedure does not require viable environmental monitoring during the initial aseptic setup of the <Redacted B4> filling line within the <Redacted B4> or during the initial aseptic setup of the <Redacted B4> automated filling machine positioned under <Redacted B4> HEPA-filtered unidirectional airflow enclosure. Per SOP-009, Environmental Monitoring of the Controlled Production Areas, environmental monitoring is not required to commence until aseptic connections setup activities have occurred. (1) On August 26, 2026, we observed operator <Redacted B4> performing set-up of the <Redacted B4> for the <Redacted B4> automated filling machine (Equipment ID # <Redacted B4> for the filling of Calcium Chloride (Lot #H24A01-26). No environmental monitoring plates were present within the ISO 5 critical area under the <Redacted B4> unidirectional airflow unit during this setup activity. (2) According to the batch record for Myer's Cocktail (Lot# G27A0S-26, Exp. 26 Nov 2026), equipment set-up of the <Redacted B4> auto filler, located inside the ISO <Redacted B4> in Suite <Redacted B4> began at 08:01. The first passive air sample was not opene

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

Specifically, {A) Your firm has not adequately demonstrated that <Redacted B4> sterilized machine <Redacted B4> parts and accessories used in aseptic filling maintain their sterile state during the established <Redacted B4> post-sterilization hold time in a controlled, non-classified area. The supporting microbiological evaluation consisted of swabbing part surfaces and incubating samples in <Redacted B4> medium <Redacted B4> for <Redacted B4> (1) Your firm has not provided adequate scientific justification that these incubation conditions are suitable for recovering and detecting microorganisms that may be encountered ifthe sterile barrier is compromised during storage within the non-classified area. {2) The provided recorded associated with the sampling, in-house incubation, and results of the swab samples lacked the following critical information: 111 Ill Ill Ill Actual incubation temperature Date and time samples were placed in the incubator Date and time samples were removed from the incubator Identity of the person who read the results

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

Specifically, (B) Batch record review of Myer's Cocktail (Lot# G27A0S-26, Exp. 26 Nov 2026) revealed that equipment set-up of the <Redacted B4> filling line, located inside the ISO-5 in Suite <Redacted B4> began on 30 July 2026 at 08:01 and was completed by Sterile Tech <Redacted B4> at 08:06 on 30 July 2026 -a total elapsed time of five minutes. However, set-up encompassed installation of <Redacted B4> chambers: <Redacted B4> where each require multiple set up steps. -For example, the <Redacted B4> chamber alone required the installation of multiple components, including the <Redacted B4>, and other associated parts.

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 w visual inspection qualification <Redacted B4> used to qualify personnel performing 100% visual inspection of injectable drug products are not adequately characterized or designed to challenge inspectors' ability to detect particulates at or near the threshold of visual detectability. For example: (A) Your firm has not established the size or size range of the particulate defects contained in the qualification units intended to challenge visual inspectors to detect the smallest contaminants possible for an inspector with 20/20 vision. Although <Redacted B4> defect vials containing particulates were submitted for size characterization, the analysis was performed using the particle-size distribution method described in USP <429>, as documented in the Certificates of Analysis. The resulting data do not establish the size of the individual particulate defect contained in each qualification unit. (B) No written procedures or records exist documenting the preparation and contents of each particulate defect unit, including particulate type, size or size range, and method of preparation. This information is known only to the individual who prepared the qualification <Red

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

Specifically, your firm assigns a <Redacted B4> beyond-use date (BUD) to Sermorelin Acetate 0.9 mg/ml Injection based on your contract laboratory stability study. However, your firm failed to provide adequate demonstration that the analytical procedure can detect relevant degradation-related changes. Your method validation report for Sermorelin Acetate, approved on August 22, 2025, does not include a mass balance assessment to demonstrate that the analytical method can adequately account for the drug substance and its degradation products, supporting the method's stability-indicating capability and reliability.

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

Specifically, (A) Your firm utilizes <Redacted B4> QA-access-controlled cabinets for the storage of sterilized machine 6 parts <Redacted B4> and accessories. <Redacted B4>. During inspection of these cabinets <Redacted B4> components, including a stopper bowl that directly contacts product stoppers, were observed without sterilization-status labels. The components lacked information identifying the applicable <Redacted B4> and sterilization date needed for personnel to determine whether the established sterile hold time had been exceeded. _____________________________ (B) Sterilization-status labels are generated by operators; however, the firm did not demonstrate a system for reconciling generated labels to the individual equipment parts associated with each sterilization cycle.

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

Specifically, (A) SOP-035, Procurement, Receipt, and Inspection of Incoming Components and Materials, does not include a sampling plan specifying the number of containers to be sampled per shipment. According to the Senior Supply Chain Manager, <Redacted B4> sent from your <Redacted B4> warehouse to your facility for sampling. Additionally, no documentation exists for the sampling performed. (B) Your firm failed to perform a specific identity test that includes a methanol limit test on each container of each lot of ethyl alcohol used as a pharmaceutical ingredient. On May 12, 2025, your firm received <Redacted B4> bottles of <Redacted B4> Ethyl Alcohol <Redacted B4> Proof (Batch # <Redacted B4> sampled, and methanol limit testing was not performed. This lot was used in the production of T-105 Injection (Papaverine Hydrochloride 30 mg/ml; Phentolamine Mesylate 1 mg/ml; Alprostadil 0.01 mg/ml), Lot #G08A10-26, BUD 04 JUL 2027. (C) Your firm failed to test each container of each lot of glycerin, used as a pharmaceutical ingredient, for diethylene glycol (DEG) or ethylene glycol (EG) contamination. Your firm did not provide a scientifically sound justification, supported by statistical

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

Specifically, a review of the batch record for Myer's Cocktail (Lot <Redacted B4>, Exp <Redacted B4> ) revealed that ingredients were added between <Redacted B4> on July 29, 2026, with no documented contemporaneous verification recorded after each individual addition. Instead, a single verification timestamp otro} ( <Redacted B4> was documented for this manufacturing step, more than two hours after the last ingredient was added.

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

Specifically, your firm failed to perform adequate smoke study videos of the biological safety cabinets (BSC) in room <Redacted B4> in a dynamic state to demonstrate unidirectional airflow and proper environmental controls during actual operating conditions. Your current practice is to perform aseptic filling operations in room <Redacted B4> with <Redacted B4> BSCs <Redacted B4> operating simultaneously. However, the smoke study videos provided, titled "Workers <Redacted B4> ISO 5 Hood During Fill," did not demonstrate that: • Unidirectional airflow is maintained during simultaneous operation oflb) <-"J BSCs • Air patterns prevent contamination of critical surfaces • Personnel movements and interventions do not disrupt the aseptic environment This is a repeat observation.

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 he firm fails to perform dissolution testing and hardness/friability testing as part of estradiol pellets batch release. The specification and batch release criteria are limited to potency assay and endotoxin testing. Since 06/01/2025 through this inspection period, approximately 260 of the <Redacted B4> batches of the following products manufactured were released without dissolution or hardness/friability testing.

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

Specifically, A. Your Quality Unit failed to implement corrective actions across all affected master batch records. For example, Master Batch Record 5.351 (Testosterone Cypionate 200 mg/mL with Miglyol, 30 mL, version 5) was revised to require documentation of filling and vent needles replaced during filling to address black particulate matter. However, this corrective action was not implemented across all affected master batch records. • 5.311: Testosterone Cypionate 200 mg/mL with Miglyol

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

Specifically, A. Equipment Calibration: Procedure 2.020, Equipment Calibration, version 4, does not include the requirement to adequately investigate the impact of equipment found out of tolerance. For example: • The most recent calibration ce1tificates for analytical balances 19-00004 (serial ~(6 (4) I, located in 1(6) (4~ and 19-00013 (serial 6) -(4) j, located in 1(0) (4)1 showed "out of tolerance" results. These balances are used as pait ofpellet compounding and vialing operations. No associated deviation or impact evaluation was perfo1med. B. Environmental Monitoring: The fnm does not have a clear and robust method for tracking and trending Inicrobial recoveries over time, resulting in inadequate monitoring of the ongoing presence of various molds in the clean rooms. For example: • Mold recoveries in the pellet compounding/pressing suiteI D) (4) increased from 0.9% in 16)14) to 24.4% in 4 lbH l with Penicillium and Aspergillus species identified (IR-2025-043). • Mol d recoverie s facility-wid e increase d from 8% in <Redacted B4> 2025 to 33% in <Redacted B4> 2025. No justification, trend report, or investigation to identify the most probable cause and conective actions was com

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

Specifically, your firm failed to perform environmental monitoring as required in SOP 4.090, Environmental and Personnel Monitoring Program, version 7, section 7 .1. This includes data, and evaluation supporting continuous <Redacted B4> non-viable particle sampling in ISO 5 and ISO 7 areas, regardless of batch manufacturing activities.

Test devices are deficient in that instmments not meeting established specifications are used.

Specifically, analytical balance <Redacted B4> calibrations and/or <Redacted B4> verifications do not cover the full bracketed range of use for the pellet process weights <Redacted B4> to <Redacted B4>. For example: • Analytical balance 19-00003 (serial <Redacted B4> was calibrated on 04/13/2026 at <Redacted B4> to <Redacted B4>. This balance is used for the pellet compounding process in <Redacted B4> This is a repeat observation *DATES OF INSPECTION 8/24/2026 (Mon), 8/25/2026 (Tue), 8/26/2026 (Wed), 8/27/2026 (Thu), 8/28/2026 (Fri), 8/31/2026 (Mon), 9/01/2026 (Tue), 9/02/2026 (Wed), 9/03/2026 (Thu), 9/04/2026 (Fri), 9/08/2026 (Tue)

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

Specifically <Redacted B4> operational/dynamic certification of the <Redacted B4> Vial Filling, Stoppering and Sealing, Machine, ISO 5 <Redacted B4> Filling Line <Redacted B4> cleanroom suite does not represent routine production operations. For example ISO 5 Filling Line was not fully assembled or in­operation, and there was one cleanroom technician outside the <Redacted B4> during dynamic nonviable particulate (NVP) monitoring. We observed up to <Redacted B4> technicians inside the ISO 7 buffer room for line ISO 5 <Redacted B4> during filling of Lidocaine 2% Injection, IO mL vial, batch 2608002. Records reviewed included: Project AZ-MVDT26l801 C-1, <Redacted B4> Cleanroom Testing and Certification, dated April 2026; and Project AZ-MVDT251301C-L Cleanroom Suite Certification, dated October 2025. All sterile drugs are manufactured on ISO 5 Filling Line <Redacted B4> personneL line setup, and production operations inside the ISO 5 <Redacted B4> are the same for aseptically filled and <Redacted B4> sterilized drugs. Examples of aseptically filled drugs include Lorazepam injection USP, 2 mg/mL, lot 2510002; and Lorazepam lnjection USP. 2 mg/mL. lot 2511001.

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

Specifically, Autoclave Qualification and routine monitoring of the <Redacted B4> equipment ID #PE00I , is deficient. ~-~~--- A There is inadequate written justification to place <Redacted B4> in the <Redacted B4> as the only process verification for routine sterilization loads. The rationale for the location of the <Redacted B4> within the <Redacted B4> is inadequate. B . Operators do not use Biological Indicators (Bis) <Redacted B4> sterilization <Redacted B4>. The approved procedures only require Bis during <Redacted B4> qualification of <Redacted B4> loads. The most recent <Redacted B4> (qualification is documented in ) 4 .PQ.0004, Perfomance Qualification <Redacted B4> Report, <Redacted B4> PE00 1, report approved 06/19/26. C. Your procedures only require a <Redacted B4> air removal test during <Redacted B4> qualification of the <Redacted B4> . Technicians do not perform <Redacted B4> tests before any routine <Redacted B4> cycles. There is inadequate written justification for the frequency of air removal tests. Technicians use <Redacted B4> PE00l to <Redacted B4> sterilize finished drug products and sterilize reusable product-contact parts, <Redacted B4> tubing, <Redacted B4>.

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

Specifically, <Redacted B4> Systen A. W e obse rv ed a leaking diaphragm v alve after the final <Re dacted B4> st ep on the <Re dacted B4> skid used, <Redacted B4> for all sterile injectab le drugs that contai n <Redacted B4> Ex amples of drugs that contain <Redacted B4> from this system include: • Ketamine 10% USP. 100 mg/mL, 5 mL, SDV. lot 2602003 • Lidocaine HCl 1 %/Epinephrine Bitartrate 10 mcg/mL Injection USP, 10 mL, SDV, lot 2603001 • Albuterol Sulfate 0.5%, 10 mL, lot 2512002 • Bupivacaine Hydrochloride 0.5%/Epine phrine Bitartrate 5 mcg/mL Injection 10 mL vial lot 2608001 B. There is an approximately one-foot-long <Redacted B4> connected to the <Redacted B4> for the <Redacted B4> on the <Redacted B4> System. <Redacted B4> contains a <Redacted B4> from the <Redacted B4> System.

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

Specifically Particulate Matter A. Production processes, procedures, and equipment do not adequately exclude particulates and other potential contaminants from sterile injectable and oral inhalation drug product vials. I reviewed the two most recent <Redacted B4> reports for Trending of Visible Particle at Visual Inspection. The trend reports include result from 100% visual inspection ruled AQL inspection of finished sterile drug vials. a. PROT.GSP.0025, Visible Particle Trending August-Dec 2025, approved 02/03/26, documents personnel found visible particulates in multiple vials from all <Redacted B4> batches manufactured and inspected during the review period. The number of vials rejected for particulate matter ranged from <Redacted B4> (0.03%) to <Redacted B4> (0.46%) vials in batches that were released. b. PROT.GSP.0035, Visible Particle Trending January 2026-June 2026, approved 08/18/26, documents personnel found visible particulates in at least one vial from all <Redacted B4> batches manufactured and inspected during the review period. The number of vials rejected for particulate matter ranged from <Redacted B4> (<0.01 %) to <Redacted B4> (0.16%) vials. B. There is no written

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

Specifically, Growth Media A. QC microbiology personnel use Standard Methods <Redacted B4> (Plate Count <Redacted B4> for all <Redacted B4> bioburden samples. There is inadequate justification to use this high <Redacted B4> instead of <Redacted B4> designed to recover microorganisms from low <Redacted B4> <Redacted B4> systems. Growth promotion on the manufacturer COA for Plate Count <Redacted B4> only lists Staphylococcus aureus, Escerichia coli, and Enterococcus faecalis. It does not include waterborne pathogenic microorganisms of interest such as B. cepacia or P. aemginosa that are knwn to colonize high purity <Redacted B4> systems. B. The firm accepts Plate Count <Redacted B4> plates based on manufacturer COA and does not perform growth promotion before use. Nitrogen Your firm uses nitrogen for pre-gassing vials and blanketing drug product solution in all lots of Lidocaine/Epinephrine Injection, Bupivacaine/Epinephrine Injection, and Lorazepam Injection. We observed multiple apparent deficiencies related to nitrogen. C. There was inadequate written justification to confirm that <Redacted B4> testing of nitrogen generated in-house ensured the nitrogen met all applicable standard

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 (21 CFR 211.165(a)).

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

Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).

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

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 conduct appropriate laboratory testing, as necessary, for each batch of drug product required to be free of objectionable microorganisms (21 CFR 211.165(a) and 211.165(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 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 test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

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

Based on the areas inspected, the people met and the documents reviewed, and considering the findings of the inspection, including the observations listed in the Inspection Report, SCL Lifesciences Limited, located at Derabassi-Barwala Road, Village Bhagwanpura, District Sahibzada Ajit Singh Nagar, Tehsil Derabassi, Punjab 140 507, India was considered to be operating at an acceptable level of compliance with WHO GMP Guidelines for APIs. All the non-compliances observed during the inspection that were listed in the full report as well as those reflected in the WHOPIR were addressed by the manufacturer to a satisfactory level prior to the publication of the WHOPIR. This WHOPIR will remain valid for 3 years, provided that the outcome of any inspection conducted during this period is positive.

SCL Lifesciences Limited has established a quality management system (QMS) to ensure the safety, efficacy, and quality of its manufactured products. The manufacturer has a quality unit independent of production that fulfilled both QA and QC responsibilities. A list of qualified personnel was identified for the release of batches of finished API and saleable intermediates. The QMS was managed manually, whereas logbooks for various QMS elements, such as change controls, deviations, OOT and OOS were managed in the ERP. Product Quality Review (PQR) The SOP for annual product review was reviewed. …

Mr. Parveen Goyal is the chairman and managing director of the company, and the department heads of VP Quality, Chief Business Officer, Chief Operating Officer, Chief Scientific Officer, Head of HR & Admin, and Director (his son, Mr. Saurav Goyal) report directly to him. Function # of personnels Production 286 Quality Control 70 Quality Assurance 34 Warehouse 17 Human Resource/Admin 12 Engineering 70 Finance and Accounts 10 Purchase 6 R&D and ARD 72 Regulatory Affairs 5 Information System Development 4 Projects 12 MSTG / Tech. …

The manufacturing site has a total land area of 11 acres. There were 3 intermediate blocks, 9 pharma blocks, 1 pressure vessel block, 1 solvent recovery block, an engineering and warehouse block, a separate QA-QC, an R&D building, and an HR Admin Block. A separate solvent storage facility was also provided. A tank farm area with underground tanks for solvent storage was also available. The site has its own drainage system supported by an ETP (Effluent Treatment Plant). …

During the visit to the synthesis and powder processing areas, it was noted that the manufacturing site was equipped with various reactors, filters, centrifuges, tray dryers, multi-mill, sifter, rotacone dryers, etc. The deficiencies raised from this section have been adequately addressed, and the same will be verified during future PQ inspections.

The documents related to the manufacturing of intermediates and APIs were prepared, reviewed, approved, and distributed in accordance with written standard procedures. A hybrid document management system was followed. In a hybrid system, some documents were kept in hard copy, while others were generated electronically via the ERP application. The deficiencies raised from this section have been adequately addressed, and the same will be verified during future PQ inspections.

The SOP for vendor qualification was discussed. The materials were categorized into key starting materials, reactants, and general materials. The QA team performed the initial assessment before vendor samples were tested. The results were forwarded to R&D for manufacturing trial batches before the supplier was approved. Key starting materials (KSMs) and primary packaging materials were audited on-site once every 3 years, whereas the rest were every 5 years. Vendor qualification of Diethyl Carbamoyl Chloride was performed by QA. The manufacturer was based in Gujarat, India.

The inspector visited the manufacturing area, Pharma II, where the WHO prequalified DEC was produced. The manufacturing area was spread over three floors. Dispensed raw materials were transferred to the second floor via elevator/hoist. The second floor housed 4 SS and GLR reactors; the first floor had 3 reactors; and the ground floor had 5 centrifuges, 2 tray dryers, 1 pressure filter, and other equipment. The entrance to Pharma II was shared by staff and visitors, whereas a separate entry was provided for materials. …

The SOP for blending of material (more than one batch) was applied to APIs and intermediates. The definition of blending was provided in the procedure, which described the methodology for performing it. As per the procedure, blending shall be carried out in accordance with the approved BPCR. The procedure stated that OOS batches will not be blended with approved batches. The deficiencies raised from this section have been adequately addressed, and the same will be verified during future PQ inspections.

The solid warehouse was briefly visited, and it was noted that incoming materials were stored there, with controlled access. The materials were quarantined before sampling was performed by the quality control laboratory. The RLAF was used to sample polybags. Three dispensing areas were provided for charcoal, primary packaging materials, and other materials. For routine manufacturing, KSM was sampled as per √n+1. The deficiencies raised from this section have been adequately addressed, and the same will be verified during future PQ inspections.

The inspector visited the QC laboratory, which was equipped with sophisticated instruments such as HPLC, GC, IR Spectrophotometer, UV Spectrophotometer, Polarimeter, Total Organic Carbon Analyzer, Auto-titrator (KF), Analytical Balance, FTIR, Melting Range Apparatus, pH Meter, Malvern Mastersizer, and Conductivity Meter. HPLC & GC instruments were supported by the Empower 3.6.1 server, and all systems were backed up. Out of specifications (OOS) The SOP for handling OOS was reviewed. …

The validation master plan was reviewed. In general, the VMP included most elements of qualification and validation activities. Requalification was carried out every 5 years for all production equipment. For the quality control equipment and instruments, qualification was a one-time activity, whereas preventive maintenance was performed every 6 months and annually. Similarly, a calibration schedule for the QC equipment and instruments was available, with calibrations performed monthly, quarterly, and half-yearly. …

The SOP for change management provided guidance on implementing changes, conducting assessments, performing risk assessments, and categorizing them. The QA was overall responsible for managing changes, including those related to the document control system. The changes were classified into major, moderate, and minor. There were two types of change: permanent and temporary. The change controls were tracked using the ERP system. The tracking of changes was done using the ERP system. …

Reprocessing, reworking, and recovery of finished APIs or intermediates were discussed. Unique numbers were given to reprocessed and reworked batches. For solvent recovery, the procedure is batch- driven. For DEC, although DMF provided a tentative procedure, the manufacturer has not performed any reprocessing. For rework, the manufacturer performed no rework. It was noted that IPA and Acetone were recovered from Stage III and IV, respectively, during the manufacturing of DEC. …

A market complaint was received from a customer regarding the drum’s lid. The investigation included a review of the batch records and concluded that everything was in order on the manufacturer’s end, whereas the logistics provider did not handle the material appropriately. The investigation was further extended using a fish-bone diagram. The SCL decided to replace the container lid to provide better protection. The deficiencies raised from this section have been adequately addressed, and the same will be verified during future PQ inspections.

The manufacturer confirmed that Diethylcarbamazine (citrate) is manufactured on-site, with no part of it produced outside. The manufacturer used a contract laboratory for performing the XRD test. The deficiencies raised from this section have been adequately addressed, and the same will be verified during future PQ inspections.