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Resultados de la investigación: Pruebas de verificación de control positivo mediante pruebas rápidas de carga biológica

rylee.lay@veolia.com — Fri, 24 Apr 2026 20:41:02 +0000

Research Findings: Positive Control Verification Testing Using Rapid Bioburden Testing rylee.lay@veolia.com Fri, 04/24/2026 - 16:41

April 24, 2026

Demonstrating Correlation of Alternative Microbiological Method to Traditional Plate Count Method

The pharmaceutical industry is increasingly seeking modern microbial methods (alternative microbiological methods) to comply with evolving regulatory standards like Annex 1 for contamination control and to improve efficiency. A critical aspect of adopting alternative methods is demonstrating their correlation to traditional plate counts, often involving a variety of microorganisms, such as those outlined in USP <61>, USP <62>, E.P. 2.6.12, EP 2.6.13 and JP 4.05.

This research presents a comprehensive comparison study to evaluate the performance of the Sievers Soleil Rapid Bioburden Analyzer against the compendial method involving 11 microorganisms and a combination of common water isolates, which are tested across multiple laboratory sites, analysts, and instruments. This research was originally presented as a poster at the PDA Pharmaceutical Microbiology Conference.

The Sievers Soleil microorganism verification study aligns with parameters mentioned in USP <1223> "VALIDATION OF ALTERNATIVE MICROBIOLOGICAL METHODS". The results demonstrate:

The Sievers Soleil Rapid Bioburden Analyzer successfully detects and quantifies Gram-positive, Gram-negative bacteria, yeasts, and molds, showing strong correlation with traditional plate counts in ultrapure water (UPW)
Performance across key metrics including accuracy, linearity, precision, range, robustness, and ruggedness, with a Limit of Detection (LOD) of 5 CFU/100 mL
The Sievers Soleil is a reliable, rapid, and sensitive microbial enumeration method for pharmaceutical water testing

Background: Implementing Modern Microbial Methods (MMMs) for Annex 1 Compliance

The publication of Annex 1 sparked increased interest among pharmaceutical companies in implementing Modern Microbial Methods (MMMs). MMMs represent a significant advancement toward obtaining bioburden results to enable proactive decision-making, instead of reactive.

Alternative rapid micro methods offer a promising alternative to traditional plating methods by enhancing efficiency and reliability in microbial testing. However, comprehensive correlation studies and adherence to pharmacopoeial guidelines, such as USP <1223> criteria, remain essential to ensure their efficacy and reliability for widespread adoption.

When selecting an MMM as a process analytical technology (PAT), it is crucial to ensure correlation with traditional methods.

Global pharmacopoeias recommend comparing results from alternative methods to compendial methods, typically using common microorganisms. The Japanese Pharmacopoeia specifically suggests using microorganisms in a starved state to simulate real-world contamination events.

In response to these guidelines and industry needs, a comprehensive comparison study was conducted between the Sievers Soleil Rapid Bioburden Analyzer and traditional bioburden test plating methods. This extensive study involved:

11 individual microorganisms and a mixed culture
Two laboratory sites
Six analysts
Six instruments

The evaluation followed USP <1223> (Validation of Alternative Microbiological Methods) guidelines, assessing:

Range
Linearity
Robustness
Precision
Reproducibility
Ruggedness

This research presents the methodology, results, and conclusions of the correlation study, demonstrating the efficacy and reliability of the Sievers Soleil Rapid Bioburden Analyzer as an alternative to traditional plating methods in pharmaceutical microbial testing.

Study Design: Comparison of Traditional Plating Methods to Rapid Bioburden Analysis for Bioburden Detection

As part of the daily start up, Negative Controls and System Suitability Standards were run and had to pass the acceptance criteria before testing could begin.

Working stock solutions were created for the following organisms:

A. brasiliensis
B. cepacia
B. diminuta
B. subtilis
C. albicans
E. coli
P. aeruginosa
R. pickettii
S. aureus
S. enterica
S. maltophilia
Mixture of B. diminuta, R. pickettii, S. maltophilia, & B. cepacia

Sample Preparation:

Concentrations targeted at 0.05, 0.1, 1, 10, and 100 CFU/mL
Sample volumes were made in 250mL bottles then aliquoted into 100mL samples-one run on Soleil, one for plating
Serial dilutions were performed to achieve desired concentrations, and solutions were added to buffered Water For Cell Culture (WFCC) to maintain cell integrity.

Traditional Plating Method:

Agar plates were prepared using:
- Tryptic Soy Agar (TSA) for bacteria
- Sabouraud Dextrose Agar (SDA) for fungi (as directed per USP <61> and USP <62>)
Sample filtration
- Each solution filtered through a manifold onto a sterile filter
- Filter aseptically transferred to the appropriate agar plate Incubation
- Plates incubated in a cell incubator Minimum incubation period: 3 days

Note: For the 100 CFU/mL samples, flood plates were used.

Results and Conclusions: Demonstration of Detection and Quantification Per Criteria Outlined in USP <1223>

The average % recovery is detailed in the chart below. Average linearity of all organisms was 0.983 and average coefficient of variation (CV%) was 28% for Soleil and compendial plates.

The comprehensive correlation study between the Sievers Soleil Rapid Bioburden Analyzer and traditional plating methods met the criteria outlined in USP <1223>.

Detection and Quantitation: Successfully detected and quantified Gram-positive bacteria, Gram-negative bacteria, Yeasts, and Mold
Performance Metrics: Demonstrated acceptable Accuracy, Linearity, Precision, Range, Robustness, and Ruggedness
Sensitivity: Limit of Detection (LoD): 0.05 CFU/mL; Limit of Quantitation (LoQ): ≤1.0 CFU/mL

In conclusion, the Sievers Soleil demonstrated correlation to traditional plate counts in CFU/mL. The above criteria demonstrates that the Soleil is a reliable, efficient, sensitive alternative to compendial plating methods.

Modern Microbial Methods with Sievers Soleil

The Sievers Soleil Rapid Bioburden Analyzer serves as a promising complementary tool to compendial testing, delivering near real-time, actionable data with demonstrated correlation to traditional plate counts in accordance with USP <1223> guidelines. As a Process Analytical Technology (PAT) solution that empowers manufacturers to implement more robust, risk-based contamination control strategies, Soleil can enhance overall process control by enabling rapid detection of microbial excursions and triggering same-day corrective actions.

Download Now: Sievers Soleil Rapid Microbial Method Verification Testing for USP <1223>

Learn more about the Sievers Soleil Rapid Bioburden Analyzer or our entire portfolio of microbial detection solutions.

Authors:

Meg Provenzano: Meg Provenzano is the Global Product Manager for Sievers endotoxin instruments at Veolia. Tiene más de 10 años de experiencia en el sector de las pruebas de detección de endotoxinas bacterianas y ha ocupado diversos puestos en las áreas de Control de calidad, Asistencia técnica y Gestión de productos. Antes de unirse a Veolia, Meg fue gerente de productos en Charles River Laboratories. Está centrada en el cliente y disfruta de la resolución práctica de problemas, ya sea para cuestiones técnicas, asistencia para ensayos o software. Meg holds a B.S. in Marine Science and Biology from Coastal Carolina University where she focused on Bottlenose Dolphin population research.
Irma Perez: Irma Perez is a Product Applications Manager at Veolia, specializing in microbiology applications for Sievers Instruments. Tiene más de 10 años de experiencia en microbiología que abarca ciencias de la vida, ciencias ambientales, instalaciones de tratamiento de agua e instrumentación analítica. En su puesto actual, desarrolla e implementa métodos analíticos para plataformas de pruebas de endotoxinas y carga biológica. Anteriormente, Irma dirigió experimentos para el desarrollo rápido de ensayos microbiológicos de diagnóstico, incluidas las pruebas de susceptibilidad a los antibióticos y la identificación. Está impulsada por una filosofía arraigada en la administración ambiental y la responsabilidad por la salud pública. Irma holds a B.S. in Environmental Science from the University of Arizona.
Cort Lawrence: Cort Lawrence is a Lead Researcher serving as the Application Support Specialist for the Sievers Soleil instrument product line at Veolia. Desde que obtuvo su Licenciatura en Ciencias en Microbiología de la Universidad de Arizona en 1010, Cort ha trabajado en diversas capacidades como experto en la materia de microbiología, con un enfoque particular en la citometría de flujo. Conocido por su enfoque práctico de resolución de problemas, Cort se dedica al avance de la tecnología de biodetección y a ofrecer soluciones innovadoras a la industria de la biotecnología. When not in the lab, he enjoys reading, swimming, and exploring the outdoors.
Matt Shallenberger: Matt Shallenberger is a Product Application Specialist at Veolia specializing in endotoxin testing and was involved in the research and development of the Soleil rapid bioburden monitoring platform. Antes de trabajar en la industria de la instrumentación, Matt fue profesor de cursos de laboratorio en microbiología en la Universidad de Arizona. He holds a B.S in Biochemistry from the University of Arizona, with a focus on fungal genetics and industrial microbial biotechnology.
Jake Vincent: Jake Vincent is the Biodetection Specialist and Advanced Lead Researcher for the Sievers R&D group at Veolia, specializing in the development of biodetection analytical instrumentation. Vincent, un colaborador clave del analizador de endotoxinas Sievers Eclipse, fue responsable de diseñar los estándares de depósito previo que se incluyen en el dispositivo de consumo. Su experiencia se refleja en la publicación en coautoría, "Miniaturización, paralelización y automatización de la detección de endotoxinas mediante microfluidos centrífugos", que apareció en Analytical Chemistry. Antes de ocupar su puesto actual, Vincent contribuyó a los métodos analíticos para las pruebas de la vacuna contra el flavivirus en Inviragen y Takeda Vaccines, incluida la realización de pruebas de ensayos clínicos para la vacuna contra el dengue Qdenga. He holds a B.S. from Colorado State University.
Gary Silver: Gary Silver is an Advanced Lead Researcher in the R&D group at Veolia, specializing in the development of biodetection analytical instrumentation. Como colaborador clave del analizador de endotoxinas Sievers Eclipse, Gary fue responsable del desarrollo y la validación de los procesos de fabricación, la metodología analítica y la estabilidad del producto. Antes de unirse a Veolia, Gary trabajó 20 años en la industria biofarmacéutica, con diversos puestos en las áreas de investigación y desarrollo, control de calidad y control de calidad. He holds a PhD in Chemistry from the University of Colorado, where his research focused on biochemical pathways and mechanisms of hydrocarbon emissions from aspen trees.
Anne Little: Anne Little is a Project Engineer supporting the Sievers Instrument product line at Veolia. Es licenciada en Biología y Química por la Universidad Estatal de Colorado-Pueblo. Anne's career has taken her through multiple sectors, beginning in water treatment before transitioning to the pharmaceutical industry.

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Resumen de la normativa: USP <645> "Conductividad del agua"

rylee.lay@veolia.com — Tue, 17 Mar 2026 03:29:13 +0000

Regulations Overview: USP <645> "Water Conductivity" rylee.lay@veolia.com Mon, 03/16/2026 - 23:29

March 16, 2026

What is USP <645> and why does it matter?

USP <645> is a general chapter in the United States Pharmacopeia (USP) that provides procedures for measuring the conductivity of water. It establishes specific test methods and acceptance criteria for different types of pharmaceutical water including purified water (PW), water for injection (WFI), water for hemodialysis, and other sterile waters.

Electrical conductivity is a measure of a substance's ability to transmit electric charge. En las aplicaciones de calidad del agua, la conductividad es el resultado del material iónico disuelto. En los sistemas de agua farmacéuticos altamente controlados, los cambios en la conductividad a menudo indican contaminación, aunque la conductividad también sirve como un indicador de la composición, la química y la consistencia del agua. Because of the relative speed and ease of measuring conductivity, this parameter has long been regulated in many applications and is widely used as an early indicator of water quality changes.

Salts, dissolved carbon dioxide (CO2) and high pH levels increase ions in solution, thereby increasing conductivity. Fluctuations in this measurement indicate the presence and level of ionic impurities, providing data about contamination in the sample.

USP <645> works in tandem with USP <643> "Total Organic Carbon", which details the monitoring of organic carbon present in a sample. En conjunto, estas pruebas de límite químico esenciales determinan si existe suficiente control en el sistema de purificación de agua. El carbono orgánico total y la conductividad proporcionan evaluaciones no específicas de la calidad del agua, lo que significa que no identifican especies contaminantes específicas, sino que miden clases enteras de contaminantes. This pair of tests quantifies contamination levels that could indicate microbial growth, residues from insufficient cleaning processes, or other impurities.

Conductivity, TOC, endotoxin and bioburden comprise four critical parameters that must be monitored to ensure PW and WFI meet compendial requirements for quality control (QC).

Download Now: Conductivity and TOC Sampling - Standard Operating Procedure (SOP) for Pharmaceutical Grade Ultrapure Water

Conductivity and TOC monitoring provide necessary information to confirm PW and WFI production is free of process by-products. Por ejemplo, si bien los tratamientos de preacondicionamiento, como el ozono y la electrodeionización (EDI), reducen la contaminación, pueden aportar contaminantes si no se gestionan adecuadamente. Conversely, while physical processes such as reverse osmosis and ultrafiltration do not introduce substances to the water, monitoring ensures these systems remain functional and effective.

Who is impacted by USP <645>?

USP <645> affects facilities who produce pharmaceutical-grade waters, use these waters as an ingredient, and instrument manufacturers.

Industries and sectors impacted by USP <645> include:

Pharmaceutical and biopharmaceutical manufacturers
Medical device manufacturers Ingredient manufacturers
Research and development facilities and research institutions
Contract testing and quality control laboratories
Water purification system and instrument manufacturers
Some healthcare and veterinary facilities

Additionally, Engineering Design Consultants (EDCs) and Engineering, Procurement, and Construction (EPC) contractors serving life science industries should take these regulations into consideration for point-of-use testing.

Note: This list is not exhaustive.

USP <645> overview and Stage I, II, and III testing

Testing methods detailed in USP chapter 645 follow a staged process of increasing complexity. Se adaptan a escenarios de prueba en línea y fuera de línea con consideraciones para determinar la idoneidad del contenedor de muestras. It should be noted that Stage 1 is required for all samples, while Stages 2 and 3 are utilized only when a sample fails to meet Stage 1 test limits.

For pharmaceutical manufacturers, the most desirable state for compliance with USP <645> is Stage 1 conductivity testing. Es el más sencillo de ejecutar y el que requiere menos tiempo por muestra. La automatización de las pruebas USP <645> de la etapa 1 ofrece un ahorro de tiempo significativo, así como una mayor integridad y seguridad de los datos. Currently, there is no readily available automation solution for Stage 2 or Stage 3 testing.

Conductivity limits for Stage 1 range from 0.6 µS/cm at 0°C to 3.1 µS/cm at 100°C with specific conductivity requirements detailed in 5° increments. If the measured conductivity exceeds the table value, testing must proceed to Stage 2.

Stage 2 conductivity details testing procedures such as temperature adjustments, agitation, and observation in order to document the change in conductivity due to uptake of atmospheric carbon dioxide. Si la lectura es inferior a un neto de 0,1 μS/cm por 5 minutos, se anota la conductividad. El límite de conductividad para la etapa 2 es de 2,1 μS/cm. Conductivity measurements at this stage may be temperature-compensated to 25°C. If this limit is exceeded, testing must proceed to Stage 3.

Stage 3 is performed within five minutes of the Stage 2 conductivity determination. La temperatura de la muestra se mantiene a 25±1 °C con la adición de cloruro de potasio. El pH se determina con la unidad de pH 0.1 más cercana. The conductivity limit is determined at the measured pH value. pH-dependent conductivity limits range from 4.7 µS/cm at pH 5.0 to 4.6 µS/cm at pH 7.0, with conductivity requirements detailed in increments of 0.1 of pH.

Download Now: Best Practice for Analyzing Compendia Water Samples for USP <643> and <645>

Download Now: Electrical Conductivity, Temperature Dependence and Instrument Methodology

USP <645> sampling methods

As mentioned above, USP <645> regulations accommodate both online and offline (laboratory) testing.

Online testing for USP <645>

Online testing involves measuring samples using an instrument with an integrated conductivity cell. Las muestras se recopilan y analizan automáticamente, mientras que los datos se registran sin problemas, lo que proporciona un monitoreo continuo. Esto se aplica solo a las pruebas de la Etapa 1. Stage 2 and Stage 3 testing are performed infrequently, and are not online tests.

Download Now: Conductivity and TOC Sampling Standard Operating Procedure (SOP)

Download Now: Low Level Linearity Conductivity Study

Offline or benchtop testing for USP <645>

Offline applications typically rely on portable meters or laboratory-based testing, where a quality control analyst gathers samples to perform periodic measurements. While compliant, the choice of analytical approach or instrument selection can significantly impact efficiency and data integrity.

For example, when conductivity measurements are made using a meter and probe, analysts sample and capture data manually, which increases the potential for transcription errors and reduces lab efficiency. Estas preocupaciones se pueden abordar mediante el uso de instrumentos de banco que analizan la conductividad y el carbono orgánico total (TOC) simultáneamente utilizando el mismo vial de muestra. This approach offers significant efficiency gains, improved data integrity, and fewer opportunities for error.

USP <645> does not make specific recommendations for process development, testing location, testing frequency, or instrument selection. These choices should be based on suitability, manufacturing process, and intended use.

Download Now: Conductivity Bridge Study: From Benchtop Meter and Probe to Automated Analysis

USP <645> Conductivity validation and verification

The regulation is instrument-agnostic, but mandates cell constant verification for all methods. Additionally, the chapter does not explicitly specify verification frequency or concentration levels, but regular verification is compulsory to ensure compliance.

The cell constant must be known within ±2% accuracy and can be verified through two approaches:

Directly, using solutions of known or traceable conductivity
Indirectly, by comparing instrument readings with conductivity sensors having known or traceable cell constants

When necessary, cell constant adjustments should follow manufacturer protocols, with verification frequency determined by sensor design characteristics.

Several factors can compromise conductivity stability, with atmospheric CO2 being a primary concern. A niveles bajos de conductividad, las muestras son particularmente susceptibles a informes erróneos debido a los efectos de absorción y desorción de CO2, que pueden introducir sesgos de medición no deseados. In contrast, higher-level samples are less immune to dissolved CO2 impacts but the compendial acceptance criteria of ±2% from stated values becomes more representative of actual instrument performance when using reference materials at elevated conductivity levels.

Resistance measurement calibration provides additional verification by replacing conductivity sensor electrodes with NIST-traceable precision resistors (accurate to ±0.1%). The measured conductivity with traceable resistors must fall within ±0.1 μS/cm of calculated values, requiring instruments to maintain minimum resolution of 0.1 μS/cm on the lowest range.

System verification ensures proper performance by comparing conductivity readings between the user's system and external calibrated devices. Values should be within ±5% of each other or meet acceptable differences based on water criticality and conductivity ranges, with sensors positioned to measure identical samples under the same temperature and water quality conditions.

Many companies that must comply with USP <645> go beyond basic compendial cell constant verification by implementing method suitability checks using different concentrations and acceptance criteria based on process capabilities. Estas comprobaciones adicionales no son requisitos reglamentarios, pero proporcionan a los establecimientos una confianza adicional en la idoneidad del instrumento para métodos específicos. These voluntary methods are separate from mandatory compendial verifications and should not be treated as a stand-in for compendial assessments.

Can you test for conductivity at the same time as TOC?

Conductivity and TOC can be tested simultaneously from the same sample vial, but typically they require different analytical methods and instruments. The tests are compatible and do not interfere with each other when performed on the same sample.

Performing simultaneous Stage 1 conductivity and TOC testing from the same vessel requires that the vessel not contribute in any significant way to either conductivity or TOC. Additionally, the vial must minimize ionic and organic contamination for compliance with USP <645> and USP <643>.

Download Now: Lean and Efficient Labs Need Simultaneous Testing for TOC and Conductivity

Download Now: Case Study: Improved Efficiency and Lower Costs Using Simultaneous Testing for TOC and Conductivity

Learn More: Standards and Vials

Download Now: Dual Use Conductivity and TOC (DUCT) Vials

We can support you with USP <645> compliance

Our experts can provide guidance on selecting appropriate instrumentation, applying proper testing procedures, and establishing effective SOPs for documentation and compliance.

After selecting suitable and compliant technology, comprehensive instrument qualification and method validation must be completed before data can be used for making quality decisions. Nuestra experiencia líder en la industria garantiza que cuenta con el respaldo de estrategias exhaustivas de implementación y validación de métodos. With decades of specialized experience, we have refined these processes to meet the most stringent regulatory requirements while maintaining operational efficiency.

Modern efficiency improvements now enable dual testing of conductivity and TOC for compliance with USP <645> and USP <643> from a single sample using specialized vials that prevent ionic leaching and CO2 contamination. This approach enhances sample integrity while reducing analysis time, when compared to traditional methods.

Additionally, many facilities have adopted online water monitoring for real-time release testing (RTRT), eliminating the need for manual sampling and streamlining the QC process. This implementation of process analytical technology (PAT) provides immediate measurement of quality attributes and demonstrates process control in a validated state, particularly when using compatible membrane conductometric technology.

Download Now: Sievers M9: Ensuring Compliance with EP Water Monographs, EP 2.2.38, and USP <645> Conductivity Regulations

Download Now: Sievers M9 Analyzers Offer Simultaneous TOC and Conductivity Compendia Compliance Testing

Download Now: Low-Level Third-Party Conductivity Standards

Tony Saavedra, MBA: Tony Saavedra, MBA is the Life Sciences Product Manager for Veolia's Sievers Analytical Instruments product line, focusing on Sievers total organic carbon (TOC) software and instrumentation. Tony comenzó su mandato en la línea de productos Sievers como parte de GE Analytical Instruments en 2011 en la organización de servicio de campo y luego tuvo la responsabilidad de liderar el equipo de Servicios Técnicos de América del Norte, donde supervisó el soporte técnico, el servicio de fábrica y las operaciones del proceso de reacondicionamiento. Antes de ocupar su cargo en los productos Sievers, Tony trabajó durante 10 años en la Marina de los EE. UU., donde supervisó inspecciones de vuelo y realizó inspecciones de control de calidad y mantenimiento de complejos radares electrónicos y conjuntos de comunicaciones. Tony holds a BS in Electronic Engineering Technology from ECPI University and an MBA from Colorado State University.
Sydney Jannetta: Sydney Jannetta is a Marketing Manager at Veolia, focusing on Sievers Instruments. Sydney ha apoyado a los clientes de instrumentos de Sievers durante los últimos seis años con experiencia en aplicaciones de endotoxinas y carbono orgánico total. Ha brindado servicios de desarrollo de métodos y pruebas de viabilidad a fabricantes farmacéuticos y ha participado en más de 20 conferencias nacionales. Sydney holds a Bachelor of Science degree in Chemistry from the University of Northern Colorado..

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Resultados de la investigación: Validación de rCR en una plataforma microfluídica para pruebas de endotoxinas a través de múltiples serotipos de bacterias gram‑negativas

rylee.lay@veolia.com — Thu, 15 Jan 2026 03:35:54 +0000

Research findings: Validation of rCR on a microfluidic endotoxin testing platform across multiple Gram-negative bacterial serotypes rylee.lay@veolia.com Wed, 01/14/2026 - 22:35

January 14, 2026

The pharmaceutical industry's transition toward recombinant cascade reagents (rCR) for bacterial endotoxins testing (BET) represents a significant advancement in sustainability and reliability. However, comprehensive validation across diverse endotoxin serotypes and testing platforms remains essential for widespread adoption.

In collaboration with ACC, we conducted a comparative study examining the performance characteristics of microfluidic and traditional plate-based detection methods using recombinant reagents. This research, presented at the PDA Pharmaceutical Microbiology Conference, demonstrates equivalent performance of these platforms in detecting various bacterial endotoxin serotypes, including naturally occurring endotoxins, from multiple Gram-negative bacterial sources.

Our findings provide critical validation data supporting the use of rCR technology with an advanced microfluidic platform, addressing key questions regarding serotype recovery, platform comparability, and analytical performance. Results confirm that recombinant cascade reagents achieve effective recovery and reliability across diverse endotoxins, further validating their suitability as a robust alternative to traditional Limulus Amebocyte Lysate (LAL) reagents for endotoxin testing.

Background: rCR Technology and Endotoxin Detection Methods

Recombinant Cascade Reagents (rCR) represent a sustainable alternative to traditional LAL for bacterial endotoxin testing. Al aprovechar la tecnología recombinante, rCR replica toda la cascada LAL sin depender de recursos derivados del cangrejo herradura, alineándose con los objetivos de sostenibilidad de la industria. As adoption of rCR expands, comprehensive validation across naturally occurring endotoxins from diverse Gram-negative bacterial sources becomes increasingly critical.

This study evaluates PyroSmart NextGen® rCR performance across lipopolysaccharides (LPS) from multiple Gram-negative bacterial species using three independent commercial lots. Additionally, the investigation compares two detection platforms - the Sievers Eclipse BET Platform and traditional 96-well microplates - to assess consistency of endotoxin recovery across serotypes and evaluate each platform's performance characteristics.

Study Design: Comparison of Modern Microfluidic Platforms to Traditional Bacterial Endotoxin Testing

Study objectives:

Evaluate recovery of diverse endotoxin serotypes using ACC's PyroSmart NextGen® rCR on both the Sievers Eclipse BET Platform and 96-well microplates with Molecular Devices SpectraMax® reader
Assess platform comparability between microfluidic and traditional 96-well microplate-based detection methods
Characterize performance parameters across multiple LPS sources

Test materials:

LPS solutions created from Gram-negative microorganism strains (Microbiologics KWIK-STIKs)
Reference Standard Endotoxin (RSE) lot R172R0
PyroSmart NextGen® rCR (ACC)

Methods:

Crude lipopolysaccharide (LPS) solutions were prepared from monocultures of the following Gram-negative microorganisms:

B. cepacia, derived from ATCC® 25416™
E. coli, derived from ATCC® 8739™
P. aeruginosa, derived from ATCC® 10145™
R. pickettii, derived from ATCC® 27511™
S. enterica, derived from ATCC® 51741™
S. maltophilia, derived from ATCC® 13636™

Cultures were suspended in Water for Cell Culture (WFCC), heated, vortexed, and filtered through 0.2µM syringe filters. Las soluciones se diluyeron hasta alcanzar las concentraciones objetivo de 0.5-1.0 EU/mL. Tap water was also collected and diluted to the same target EU/mL.

As a control for the LPS extraction method, WFCC was heated, vortexed, and filtered via the same methodology and tested for interference and contamination. The WFCC control demonstrated equivalent performance characteristics as LAL Reagent Water (LRW) in assays.

Reference Standard Endotoxin (RSE, lot R172R0) was prepared across a concentration range of 50-0.005 EU/mL via serial dilution and tested as a standard curve contemporaneously alongside all samples.

Results and Conclusions:

BET Platform Equivalency and Performance Characteristics of rCR

This investigation confirms equivalent performance between the Sievers Eclipse BET Platform and traditional 96-well plate methodology in detecting various bacterial endotoxin serotypes, including naturally occurring endotoxins. Data validate the Eclipse platform's effective use of recombinant cascade reagents (rCR) for reliable recovery across diverse endotoxins.

The Eclipse's centripetal microfluidic technology provides operational advantages, including reduced assay time and decreased potential for errors. At a sensitivity of 0.005 EU/mL, the average reaction time for RSE on the Eclipse was 1,692 seconds, representing a 37% reduction compared to 2,687 seconds observed with the SpectraMax.

Key findings support the Eclipse platform as a compliant solution for endotoxin testing, offering:

Enhanced analytical efficiency with significant time savings
Decreased variability through automated microfluidic processing
Sustainable testing practices via rCR compatibility
Maintained sensitivity and accuracy across diverse endotoxin sources

These results contribute to the growing body of evidence supporting rCR adoption and advanced microfluidic platforms for pharmaceutical quality control applications.

Authors:

Veronika Wills: Veronika Wills directs Global Technical Service groups at Associates of Cape Cod, Inc. She joined the team in 2007 and has since become a globally recognized subject matter expert and public speaker on endotoxin and glucan testing. Aporta una vasta experiencia que es vital para los clientes de ACC en lo que respecta a soporte técnico para el análisis de matrices de muestras complejas, la resolución de problemas, la validación de métodos, las investigaciones y los aspectos regulatorios de BET. Últimamente, Veronika se ha dedicado intensamente a la evaluación y la implementación de tecnologías recombinantes y su automatización. Veronika holds a Master's Degree in Biochemical Engineering from the Institute of Chemical Technology in Prague, Czech Republic.
Meg Provenzano: Meg Provenzano is the Global Product Manager for Sievers endotoxin instruments at Veolia. Tiene más de 10 años de experiencia en el sector de las pruebas de detección de endotoxinas bacterianas y ha ocupado diversos puestos en las áreas de Control de calidad, Asistencia técnica y Gestión de productos. Antes de unirse a Veolia, Meg fue gerente de productos en Charles River Laboratories. Está centrada en el cliente y disfruta de la resolución práctica de problemas, ya sea para cuestiones técnicas, asistencia para ensayos o software. Meg holds a B.S. in Marine Science and Biology from Coastal Carolina University where she focused on Bottlenose Dolphin population research.
Jake Vincent: Jake Vincent is the Biodetection Specialist and Advanced Lead Researcher for the Sievers R&D group at Veolia, specializing in the development of biodetection analytical instrumentation. Como colaborador clave en el analizador de endotoxinas Sievers Eclipse, Jake fue responsable de diseñar los estándares predepositados presentes en el dispositivo microfluídico desechable. La investigación de Jake sobre detección microfluídica de endotoxinas fue publicada en Analytical Chemistry bajo el título "Miniaturization, Parallelization, and Automation of Endotoxin Detection by Centrifugal Microfluidics", donde figura como coautor. Antes de incorporarse a Veolia, Jake colaboró en el desarrollo de métodos analíticos para el ensayo de vacunas contra los flavivirus en Inviragen y Takeda Vaccines, incluyendo los ensayos clínicos de la vacuna contra el dengue, Qdenga. He holds a B.S. from Colorado State University.

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Industrial and Environmental

Optimice la configuración de energía de la electrodeionización para mejorar la calidad del agua ultrapura (UPW)

carolynstevens — Mon, 29 Sep 2025 16:25:03 +0000

Optimize EDI Power Settings to Improve Ultrapure Water (UPW) Quality carolynstevens Mon, 09/29/2025 - 12:25

September 29, 2025

How to Optimize EDI Power Settings and Performance to Improve Ultrapure Water (UPW) Quality

Introduction: What is Electrodeionization (EDI)

Electrodeionization (EDI) is a critical process in semiconductor ultrapure water (UPW) systems that combines ion exchange (IX) resins, ion-permeable membranes, and high electric potentials to remove ionic contaminants from water. El sistema funciona mediante el uso de campos eléctricos para extraer iones a través de resinas de intercambio y a través de membranas, purificando simultáneamente el agua y regenerando las resinas. While this continuous process ensures high-quality ultrapure water through real-time monitoring and voltage control, it requires significant electrical power consumption during operation.

The Importance of Continuous Contamination Control in Microelectronics Manufacturing

Ultrapure water (UPW) quality is a critical component to semiconductor fabrication and the purity of this ingredient is directly tied to wafer yield and product quality. Even trace amounts of contaminants in UPW can cause particle deposits, metal contamination, and surface defects on wafers, leading to reduced device performance and overall quality.

Continuous monitoring and control of UPW systems with tools such as total organic carbon (TOC) monitoring and boron monitoring supports high quality fabrication. With immediate process understanding, manufacturers can respond to deviations quickly and with fewer interruptions to production.

The dynamic nature of UPW systems makes ongoing monitoring particularly important. Por ejemplo, cuando se ajustan los voltajes del sistema de EDI, los niveles de contaminantes pueden tardar una semana o más en estabilizarse, tiempo durante el cual la calidad del agua del sistema puede fluctuar de manera impredecible. Los fabricantes navegan por estos períodos de transición con monitoreo en tiempo real para realizar ajustes constantes mientras mantienen la producción y la calidad de las obleas. Without this capability, the alternative is pausing production while contamination clears the system - a costly disruption that can significantly impact manufacturing operational efficiency.

In today's competitive semiconductor landscape, continuous UPW quality control has evolved from beneficial to essential for maintaining both product quality and operational profitability.

Real-time Monitoring of EDI Effluent

A study with a semiconductor facility tracked critical contaminant levels and overall UPW quality using the Sievers Boron Online UPW Ultra Analyzer and demonstrated the complex relationship between power settings and water quality parameters. Si bien se descubrió que los ajustes de potencia más altos eliminaban de manera más efectiva contaminantes como el boro y la sílice, también revelaron un inconveniente inesperado: el aumento de los voltajes de EDI promovió la formación de formas iónicas de dióxido de carbono disuelto, lo que podría conducir a una mayor conductividad en el UPW. This finding highlighted the delicate balance needed in EDI operations, as excessive power settings could not only increase energy costs but potentially compromise UPW quality.

The research established that EDI effluent quality is determined by three key factors:

Feedwater quality
Resin efficiency
EDI power settings

It yielded data that illustrates the relationship between EDI power and levels of boron, silica, and conductivity in the facility's effluent, and the monitoring helped engineers implement precise control strategies, remove contaminants, and optimize power consumption, ultimately achieving high water quality standards and operational cost efficiency.

Sievers Boron Ultra Online UPW Analyzer

The Sievers Boron Online UPW Ultra Analyzer serves as a critical tool in modern ultrapure water quality management systems. By delivering continuous monitoring and real-time detection, plants are able to prevent ionic contamination events before they become problematic.

Read the full details of the study here.

Learn more about UPW, the Sievers Boron Online UPW Ultra Analyzer, and the microelectronics industry on our applications page.

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Consejos y trucos: Volver a lo básico de los análisis de carga microbiana

carolynstevens — Tue, 16 Sep 2025 17:41:14 +0000

Tips and Tricks: Going Back to the Basics of Bioburden Testing carolynstevens Tue, 09/16/2025 - 13:41

September 4, 2025

Bioburden Testing: Traditional vs Modern

What is bioburden?

Bioburden is a measurement that refers to the total number of viable microorganisms, including bacteria and fungi, present in or on products, materials, or objects. It's particularly crucial in pharmaceuticals, medical devices, raw materials, and cosmetics, since these industries must adhere to strict acceptable limits set by regulatory agencies.

Monitoring bioburden is vital. La contaminación microbiana puede conllevar riesgos como comprometer la eficacia del producto, costosas retiradas de productos y, lo que es más importante, posibles peligros para la salud de los consumidores. Los niveles de carga biológica son un indicador clave de la calidad del proceso de fabricación. They are influenced by various factors including the manufacturing environment and equipment cleanliness and condition.

How do you test for bioburden?

Bioburden testing has traditionally relied on cultivation methods that measure Total Viable Count (TVC), combining Total Microbial Count (TMC) and Total Yeast and Mold Count (TYMC), and are reported in Colony Forming Units (CFU/mL or CFU/gram). Traditional approaches include membrane filtration, direct plating (pour plate and spread plate), and Most Probable Number (MPN).

Dating back to 1905, these traditional methods provide acceptable accuracy, but their long wait times (2-7 days) make them ineffective for real-time process monitoring and timely product release. This creates a significant gap between testing and actionable results, leading to retrospective, rather than proactive, process controls.

Rapid Microbial Methods (RMMs) offer a modern solution to this gap, delivering results in hours - or even less than an hour with specific RMMs - rather than the days required by traditional methods. Si bien no todos los métodos microbiólogicos rápidos son iguales, ciertas tecnologías de detección microbiana rápida se correlacionan bien con los recuentos en placa tradicionales, lo que las convierte en una opción ideal para los fabricantes que buscan velocidad y confiabilidad. By maintaining the accuracy technicians are accustomed to while dramatically reducing wait times, these select RMMs not only accelerate the testing process but also enhance overall operational efficiency.

With near real-time data for monitoring ultrapure water and manufacturing processes, RMMs deliver substantial improvements over traditional bioburden testing, including significant time-savings for quality control labs, faster product release cycles, reduced operational costs, and enhanced overall productivity.

The combination of speed and accuracy makes switching to RMMs suitable for both laboratory and at-line applications, offering life sciences customers a way to modernize their bioburden testing without sacrificing reliability.

How fast are rapid microbial methods?

Rapid Microbial Methods (RMMs) deliver results in hours rather than days, with speeds varying by technology. Many RMMs provide results within 8 hours, while advanced systems can deliver data in under 45 minutes - compared to traditional methods that require 2-7 days.

The fastest RMM technologies, such as flow cytometry-based systems, enable precise analysis of single cells, offering near real-time results, and in certain cases, distinguishing between viable cells and abiotic particles. This represents a dramatic improvement over traditional plate-counting methods, enabling same-day decision-making instead of multi-day waiting periods for product release and quality control decisions.

What are the benefits of modern bioburden testing methods / rapid microbial methods (RMMs)?

Speed and Efficiency
- Dramatically Faster Results - Obtain bioburden data in under 45 minutes with certain RMMs, compared to 2-7 days with traditional methods
- Near Real-Time Monitoring - Enable immediate decision-making with actionable results using RMMs that correlate to conventional plate counts
- Faster Product Release - Reduce the time products are held up waiting for test results
Operational Improvements and Cost Savings
- Enhanced Lab Efficiency - Automated systems reduce manual plate counting, minimizing human error
- Improved Decision-Making - Make fast, confident decisions about manufacturing processes to reduce risk
- Remove Testing Bottlenecks - Eliminate the bioburden testing bottleneck that delays product release
- Significant Cost Savings - Reduce costly waste from process inefficiencies or discarded products
Risk Management and Quality Control
- Better Risk Management - Make faster decisions to prevent contamination issues and reduce manufacturing risks
- Enhanced Data Integrity - Certain RMMs can provide electronic records that are easily retrievable and tamper-proof, reducing transcription errors while offering comprehensive audit trails for accuracy and regulatory compliance
- Comprehensive Monitoring - Monitor critical control points in your water system with faster, automated testing that provides real-time contamination detection

Utilizing RMMs with the Sievers Soleil

The Sievers Soleil Rapid Bioburden Analyzer is a transformative rapid microbial detection system for bioburden testing in pharmaceutical manufacturing. Funciona combinando la citometría de flujo de alto rendimiento con tinciones de viabilidad patentadas para proporcionar resultados de carga biológica casi en tiempo real que se correlacionan con los recuentos en placa. Operando a 8 mL/min (significativamente más rápido que los μL/min de la citometría de flujo tradicional), el analizador ofrece resultados en menos de 45 minutos con una sensibilidad por debajo de 10 células viables/100 mL, en comparación con los métodos convencionales que requieren entre 2 y 7 días. El sistema utiliza algoritmos sofisticados para distinguir con precisión entre partículas vivas y no vivas, lo que permite a los fabricantes farmacéuticos pasar de controles de proceso retrospectivos a proactivos. This facilitates same-day actions to minimize production delays and costly operational shutdowns while improving overall risk management strategies.

Think the Sievers Soleil Rapid Bioburden Analyzer might be a good fit for your lab? Learn more about it here:

Download now: Sievers Soleil Rapid Bioburden Analyzer Infographic

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Consejos y trucos: Volver a lo básico del carbono orgánico total y la conductividad

carolynstevens — Tue, 16 Sep 2025 16:02:12 +0000

Tips and Tricks: Going Back to the Basics of Total Organic Carbon and Conductivity carolynstevens Tue, 09/16/2025 - 12:02

September 4, 2025

The Fundamentals of Total Organic Carbon and Conductivity

What is Total Organic Carbon?

Total Organic Carbon (TOC) is an analytical measurement that indicates the amount of carbon found in organic compounds present in a sample, serving as a key indicator of water quality and purity in pharmaceutical and environmental testing. El carbono orgánico total es fundamental porque incluso trazas de contaminación orgánica pueden comprometer la calidad del producto y la seguridad del consumidor. El carbono orgánico total se origina en fuentes naturales (es decir, plantas y animales) y materiales sintéticos (es decir, productos de limpieza, plásticos y pesticidas). It's characterized by carbon-hydrogen bonds that can be oxidized to CO₂.

A common way to determine the amount of organic carbon in a sample is by subtracting results for Total Carbon (TC) and Inorganic Carbon (IC):

Total Carbon - Inorganic Carbon = Total Organic Carbon, or

TC - IC = TOC, where:

TC (Total Carbon): All carbon present in a sample, including organic inorganic forms.
IC (Inorganic Carbon): Carbon present in inorganic compounds (CO₂ , HCO₃ - and CO₃²-)
TOC (Total Organic Carbon): Amount of organic carbon remaining after the inorganic carbon has been removed.

USP <643> establishes standards and procedures for TOC testing in pharmaceutical grade water, specifying technology requirements, system suitability analysis, method validation parameters, and acceptance criteria to ensure water quality and purity.

What is Conductivity?

Conductivity measures a substance's ability to conduct an electrical current, indicating the presence of inorganic chemicals and salts. In pharmaceutical water testing, conductivity serves as a critical quality attribute to detect the presence of ionic species and ensure water purity.

Per USP <645>, conductivity levels must be below 1.3 μS/cm at 25 °C. Conductivity testing detects both intrinsic ions (from dissolved CO2) and extrinsic ions (such as chloride and ammonia), which can harm equipment and human health. Testing is crucial for monitoring salt and inorganic contamination.

Who tests for TOC and Conductivity?

TOC and conductivity testing applications by industry:

Pharmaceutical: Cleaning validation, Water for Injection (WFI), sterile water, and clean steam.
Microelectronics: Ultrapure water monitoring and process control
Municipalities: Drinking water quality, wastewater treatment, and stormwater management
Food & Beverage: Cleaning processes, wastewater monitoring, release water, and product consistency
Oil & Gas: Water contamination assessment and process monitoring

How do you measure and test for TOC and Conductivity?

TOC testing involves two critical steps: oxidation and detection. During oxidation, organic compounds in the sample are converted to carbon dioxide (CO₂) through established methods including high-temperature catalytic combustion or UV / persulfate oxidation (wet chemical oxidation). Different oxidation techniques are selected depending on application needs, sample matrices, or testing requirements.

The detection phase is where analytical precision becomes crucial, as CO₂ measurement accuracy directly determines TOC result reliability. Three primary detection methods include:

Non-Dispersive Infrared (NDIR) - Measures CO₂ through infrared light absorption but suffers from water vapor interference that compromises accuracy
Direct Conductivity - Measures sample conductivity before and after oxidation but is prone to various interferences
Membrane Conductometric Detection - Offers robust CO_² measurement while effectively minimizing interferences, providing the most reliable results

When accuracy and precision are non-negotiable, Membrane Conductometric technology enables confident water quality assessment and process control.

For conductivity, common testing methods include two-electrode (contacting) conductivity cells, four-electrode cells, toroidal (inductive) conductivity sensors, and in-line continuous monitoring systems, with measurements typically performed using conductivity meters that apply an A/C voltage across electrodes.

In pharmaceutical water testing, conductivity measurements are governed by USP <645>, which describes three stages of conductivity testing to ensure water meets stringent purity requirements. These measurements are captured temperature-compensated, or non-temperature-compensated conductivity, per the staged requirements in USP <645> to provide a complete assessment of water quality.

TOC and conductivity testing provide complementary measurements of water quality; TOC detects organic contamination while conductivity measures ionic and inorganic impurities, together ensuring comprehensive water purity assessment for pharmaceutical and industrial applications.

TOC and Conductivity with Sievers Analytical Instruments

To meet diverse customer needs, Veolia offers a wide variety of analyzers as part of its Sievers portfolio with different analytical ranges and suitability for specific applications, enabling comprehensive solutions across multiple industries. The Sievers Analytical Instruments product line includes advanced solutions for both TOC and conductivity testing.

For TOC and conductivity testing, the Sievers M500, M9, and M5310 C TOC Analyzers deploy membrane conductometric technology to measure both TOC and conductivity. The Sievers technology uses a proprietary gas-permeable membrane to filter CO₂ from samples into ultra-pure deionized water. Este proceso permite el análisis sin interferencias de otros componentes. The CO₂ transfer creates measurable conductivity changes that correlate to IC and TC levels, which allows users to calculate TOC levels.

The Sievers InnovOx TOC Analyzer uses innovative Supercritical Water Oxidation (SCWO), technology that combines heat, pressure, and chemical oxidizers to handle complex samples including oils and fats and other challenging substances.

Direct conductivity, employed by the Sievers CheckPoint TOC Sensor, measures samples before and after UV oxidation.

All of these methods, excluding the Sievers CheckPoint TOC Sensor, follow the fundamental principle of oxidizing organic compounds to CO2, measuring the resultant CO₂, and calculating TOC as the difference between total carbon and inorganic carbon. This approach ensures compliance with USP <643> requirements while providing accurate, interference-free detection.

Veolia has established itself as a leader in TOC analysis with its Sievers Analytical Instruments product line. To learn more about implementing TOC and conductivity testing in your operations, watch our on-demand webinar: https://www.watertechnologies.com/lp-ai-online-toc-for-cv-webinar

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Consejos y trucos: Volver a los conceptos básicos de las pruebas de detección de endotoxinas

carolynstevens — Tue, 16 Sep 2025 13:18:13 +0000

Tips and Tricks: Going Back to the Basics of Endotoxin Testing carolynstevens Tue, 09/16/2025 - 09:18

September 4, 2025

The Fundamentals of Endotoxin Testing

What are endotoxins?

Endotoxins are biocontaminants derived from gram-negative bacteria's outer cell membrane. Aunque no son organismos vivos en sí mismos, son fundamentales para la supervivencia de las bacterias y desempeñan múltiples funciones, como la integridad estructural y el transporte de nutrientes. Endotoxins are:

Present naturally in food and water
Dangerous if entering the bloodstream
Common in raw materials and products

Endotoxins should not be confused with bacteria themselves - they are components that become harmful when separated from a bacterial cell.

Why do we test for endotoxins?

Bacterial Endotoxins Testing (BET) is crucial because endotoxins pose serious health risks when entering the bloodstream directly, bypassing normal digestive defenses. As pyrogens (substances that produce fever when introduced or released into the blood), they can cause potentially fatal drops in blood pressure, leading to organ failure, septic shock, or even death, when introduced into the bloodstream or spinal fluid.

Particularly concerning is that endotoxins persist even after sanitization; killing bacteria doesn't eliminate the toxic threat. For these reasons, testing is essential in these key areas of pharmaceutical and medical device manufacturing:

Drug production and formulation
Cleaning validation (equipment and container sanitization)
Buffer preparation
Drug reconstitution

Given endotoxins' ubiquitous nature and resistance to standard sanitization methods, rigorous BET is vital for ensuring patient safety in medical and pharmaceutical applications.

Is endotoxin testing mandatory?

Regulatory agencies like the FDA, EMA, and others require endotoxin testing to ensure products meet safety standards and do not cause pyrogenic reactions. It is mandatory for:

Pharmaceutical manufacturers producing parenteral drugs, including:
- Intravenous (IV)
- Intramuscular (IM)
- Intrathecal (IT)
Medical device manufacturers whose products contact blood
Veterinary/animal health product manufacturers producing blood-contacting items

The specific testing requirements depend on the product type, intended use, and regulatory jurisdiction.

How do you test for endotoxins?

Bacterial Endotoxins Testing (BET) primarily uses LAL (Limulus Amebocyte Lysate), derived from horseshoe crab blood. This remarkable discovery from the 1950s was standardized in the 1960s, creating a reliable endotoxins detection method.

There are three common testing approaches used today:

Deciding which method is best to use depends on several factors, including product characteristics, sensitivity requirements, and regulatory requirements.

The newest method for endotoxins testing: Microfluidic technology

The Sievers Eclipse Bacterial Endotoxins Testing (BET) Platform is a game-changing method for endotoxin testing due to its microfluidic technology that delivers significant time savings and efficiency improvements over traditional methods. Las principales ventajas incluyen una reducción del 89 % en los pasos de pipeteo y un tiempo de preparación de apenas 5 a 10 minutos. La plataforma Eclipse utiliza una placa microfluídica para mezclar las muestras con el reactivo LAL, utilizando solo 1 mL de reactivo LAL, un 90 % menos que los métodos convencionales, manteniendo la precisión. The unique microplate contains embedded endotoxin standards and positive product controls (PPCs) and remains stable at room temperature for up to 25 months, eliminating expensive cold storage requirements.

Other unique capabilities of the Eclipse Platform include remote data review, minimal laboratory space and training requirements, and reduced failure rates. Los resultados se miden en unidades de endotoxina (UE), siendo 1 UE aproximadamente igual a 1 partes por billón (ppt). While LAL's biological nature typically requires users to prepare standard curves, PPCs, negative controls, and samples for each assay, the Sievers Eclipse significantly simplifies this process - users only need to add water and samples to the appropriate segments, as the standards and controls are already embedded in the microplate.

While traditional testing approaches work, newer microfluidic technology offers a more efficient, reliable, and cost-effective method for endotoxin testing while still ensuring regulatory compliance. La tecnología microfluídica también ofrece a los usuarios flexibilidad en la elección de reactivos, ya sea que elijan el LAL tradicional o el reactivo en cascada recombinante (rCR). This modern technology, combined with recombinant reagents, represents a key opportunity to achieve both efficiency gains and sustainability goals in endotoxin testing.

Learn more about bacterial endotoxins testing, LAL, rCR and the Sievers Eclipse BET Platform by watching a quick on-demand webinar: https://www.watertechnologies.com/lp-ai-usp-86-webinar

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Industrial and Environmental

Maximización del rendimiento de la caldera con el monitoreo de carbono orgánico: cómo el monitoreo de compuestos orgánicos protege el equipo y la rentabilidad al tiempo que aumenta la eficiencia de la caldera

carolynstevens — Thu, 04 Sep 2025 15:49:01 +0000

Maximizing Boiler Performance with TOC Monitoring: How Organics Monitoring Protects Equipment and Profitability While Increasing Boiler Efficiency carolynstevens Thu, 09/04/2025 - 11:49

September 4, 2025

Boiler systems are an integral part of countless industrial facilities across the world, from power plants and refineries to food & beverage operations and chemical processing facilities. Ya sea que generen electricidad para comunidades o apoyen procesos de fabricación críticos, estos sistemas de generación de vapor requieren agua ultrapura libre de contaminantes orgánicos para funcionar de manera segura y eficiente. However, maintaining equipment uptime and preventing unplanned costs are critical to preserving profitability and operational control in these competitive industries.

Water chemistry and boiler system performance

Proper boiler water chemistry is essential for preventing scale formation and corrosion, which can lead to costly equipment failure and unplanned shutdowns. Debido a las elevadas temperaturas y presiones propias de los ciclos de agua-vapor, incluso cantidades mínimas de compuestos orgánicos pueden degradarse y transformarse en ácidos orgánicos, lo que acelera el deterioro. Contaminants such as sugars, cleaning agents, cooling fluids, or organic acids are often present at low levels and remain undetected by traditional monitoring methods, creating hidden risks that can result in catastrophic failures.

Contamination: Sources and real-world incidents

These contaminants can originate from various sources - CO2 corrosion typically stems from issues within the boiler feedwater system itself, while glycol contamination often results from external leaks in associated heat exchangers or chiller systems. For example, CO2 entering through feedwater leads to generalized metal loss, while glycol leaks from cooling systems can contaminate steam condensate and cause severe fouling.

Recent incidents at major facilities underscore these risks. Las fugas de glicol obligaron a cerrar varias plantas de energía, mientras que una importante refinería de Texas sufrió contaminación del condensado de vapor e incrustaciones en la caldera, lo que resultó en tiempos de inactividad no planificados y grandes pérdidas financieras. For plant managers across these industries, implementing robust contamination detection systems isn't just about maintenance - it's about protecting profits, preventing shutdowns, and ensuring reliable operations.

Traditional monitoring techniques including pH and conductivity often fail to detect many common contaminants. Las fugas de glicol, por ejemplo, pasan desapercibidas debido a su estado no iónico a temperatura y presión ambiente. Unfortunately, these methods don't alert operators to organic acid degradation until damage has already occurred.

Monitoring total organic carbon (TOC) in boiler water provides a proactive solution for detecting contamination and optimizing processes. El carbono orgánico total constituye un indicador clave para detectar posibles problemas de corrosión e integridad del sistema antes de que ocurran consecuencias perjudiciales, algo que los métodos de monitoreo tradicionales a menudo no logran. El monitoreo de carbono orgánico total identificó con éxito la contaminación de glicol en plantas de energía, lo que permitió un mantenimiento proactivo que evitó costosas interrupciones. Similarly, continuous TOC monitoring at industrial facilities enables real-time detection of contamination events, protecting capital equipment and enhancing production uptime.

Maximizing condensate reuse through effective monitoring

Reusing condensate from industrial processes carries inherent contamination risks, but these risks and their financial implications can be effectively mitigated with online organics monitoring. Accurate assessment of condensate quality not only provides opportunities to detect leaks and prevent fouling, but also impacts operational decisions - enabling maximum reuse while reducing costs associated with producing additional make-up water and wastewater treatment.

The Sievers InnovOx TOC Analyzer addresses these critical monitoring needs with reliable online organics detection using advanced supercritical water oxidation technology. Este método de oxidación de eficacia comprobada alcanza una eficiencia de oxidación de más del 99 %, lo que garantiza una exactitud y precisión superiores en la medición del carbono orgánico total en toda la gama de posibles contaminantes. Al ofrecer información en tiempo real sobre la calidad del agua de la caldera, InnovOx ayuda a optimizar el rendimiento, reducir al mínimo el mantenimiento no programado y aumentar la rentabilidad. To learn more about how the Sievers InnovOx TOC Analyzer can help your boiler water system needs, read our application note.

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Learn more about the Sievers Eclipse

Hallazgos clave: Pruebas de endotoxinas bacterianas con reactivos recombinantes y tecnología microfluídica innovadora

rylee.lay@veolia.com — Fri, 15 Aug 2025 18:29:29 +0000

Key Findings: Bacterial Endotoxins Testing Using Recombinant Reagents and Innovative Microfluidic Technology rylee.lay@veolia.com Fri, 08/15/2025 - 14:29

August 13, 2025

We collaborated with Eli Lilly to present research on recombinant reagents and microfluidic technology for Bacterial Endotoxins Testing (BET) at the Parenteral Drug Association (PDA) Pharmaceutical Microbiology Conference.

Our findings, based on real-world sample data, demonstrate the accuracy and reliability of recombinant agents on modern microbiological detection platforms. Jay Bolden and Hayden Skalski present research at PDA Microbiology Conference.

Jay Bolden and Hayden Skalski present research at PDA Microbiology Conference

Background: Limulus Amebocyte Lysate (LAL) vs. recombinant cascade reagents (rCR) in microfluidic BET assays

Pharmaceutical companies are increasingly adopting innovative technologies to meet evolving regulatory expectations while building more sustainable operations. Las pruebas de endotoxinas son un excelente ejemplo de este cambio, ya que las presiones regulatorias y de sostenibilidad están transformando el panorama de BET. Annex 1 encourages technological advancement to streamline manufacturing processes, and the recent publication of USP <86> on recombinant reagents for endotoxin testing represents a key opportunity to achieve both regulatory compliance and sustainability goals.

For these reasons, Veolia, in partnership with Eli Lilly, conducted a comparison study using the Sievers Eclipse Bacterial Endotoxins Testing (BET) Platform to compare results between traditional Limulus Amebocyte Lysate (LAL) and newer recombinant cascade reagents (rCR). La plataforma utiliza microfluidos y fuerza centrípeta; permite la preparación del ensayo en el 85% del tiempo que se tarda en montar una microplaca tradicional de 96 pocillos; utiliza hasta un 90% menos de LAL o rCR; y automatiza la entrega del LAL a las muestras. Beyond increasing efficiency, it assures precise and accurate results, allowing manufacturers to meet Annex 1 and sustainability goals while remaining in full compliance with regulations to assure patient safety.

This research outlines the results of the endotoxin tests with data obtained from real-world samples, providing a practical comparison between the two reagent types.

Comparison Study: Detecting naturally occurring endotoxins (NOE) and Reference Standard Endotoxin (RSE)

The purpose of this study was driven by two objectives. El objetivo principal fue evaluar la detección y recuperación tanto de endotoxinas de origen natural (NOE) como de agua purificada enriquecida con endotoxina estándar de referencia (RSE). This evaluation was conducted using two different testing methods: traditional Limulus Amebocyte Lysate (LAL) and recombinant Cascade Reagent (rCR), with the goal of demonstrating reliable endotoxin recovery across both testing platforms.

Secondly, these capabilities were validated on the Sievers Eclipse BET platform by challenging it with both types of reagents. This validation was particularly significant as it aimed to demonstrate the system's suitability for real-world sample testing while offering two substantial benefits: a 90% reduction in reagent consumption and the option to use recombinant reagents, thereby promoting more sustainable testing practices in the industry.

Samples: rCR comparison study of 12 sample types

The following samples were used in the comparison study between Limulus Amebocyte Lysate (LAL) and recombinant Cascade Reagents (rCR):

Two monoclonal antibodies
Insulin
Peptide
NOE (see Figure 1)
Histidine and Sodium Acetate
LRW
Purified Waters
Purified Waters with RSE spikes
Polysorbate 80
Counterfeit products
Components (stopper, cartridge)
Yeastolate

Figure 1: Comparison of Naturally Occurring Endotoxins (NOE)

Results: LAL vs rCR - Performance and testing results

The following figure details Positive Product Control (PPC) recovery rates of sample and reagents.

Figure 2: Percent Recovery Comparison of Sample and Reagent

Conclusion: rCR performance in microfluidic platforms

This study showed equivalent performance between LAL and rCR using the Sievers Eclipse for the detection of bacterial endotoxins in real-world samples, as well as naturally occurring endotoxins. Based on the evidence, it can be determined that the Sievers Eclipse Bacterial Endotoxins Testing Platform is able to successfully utilize recombinant Cascade Reagents, provided that the sample's compatibility has been verified.

Automation via the Eclipse's centripetal microfluidic platform offers the simplest form of BET microfluidics available, providing significant time savings and reducing opportunities for error. With the availability of this innovative technology, BET assays can be streamlined while remaining fully compliant with compendia.

Benefits include:

USP <85> and <86> compliant
Proven to work with both LAL and rCR reagents
Up to 90% less reagent needed; aids in sustainability initiatives
27 total pipetting steps for 21 samples for increased efficiency
Innovative technology aligned with Annex 1 guidelines

Authors:

Jay Bolden: Jay Bolden is a Senior Director in the Eli Lilly and Company global Analytical Quality Control Organization. Es un experto en la materia de endotoxinas bacterianas y dirige un equipo con supervisión de control de calidad global para endotoxinas, microbiología y métodos de prueba virológicos. Jay tiene una licenciatura en Biología y un certificado en Estudios Ambientales de la Universidad de Indiana y tiene más de 25 años de experiencia en la industria en desarrollo, microbiología de procesos y laboratorio, y liderazgo en laboratorios de microbiología. Jay es miembro del Comité de Expertos en Microbiología de la Farmacopea de los Estados Unidos y es autor de un capítulo de libro y de varios artículos revisados por pares sobre endotoxinas. Accordion content 1.
Meg Provenzano: Meg Provenzano is the Global Product Manager for Sievers bio-detection instruments at Veolia. Tiene más de 10 años de experiencia en el sector de las pruebas de detección de endotoxinas bacterianas y ha ocupado diversos puestos en las áreas de Control de calidad, Asistencia técnica y Gestión de productos. Antes de unirse a Veolia, Meg fue gerente de productos en Charles River Laboratories. Está enfocada en el cliente y disfruta de la resolución práctica de problemas, ya sea para cuestiones técnicas, asistencia para ensayos o software. Meg holds a B.S. in Marine Science and Biology from Coastal Carolina University, where she focused on Bottlenose Dolphin population research.
Brian Short: Brian Short is a Global Pharmaceutical Application Specialist at Veolia, providing strategic pharmaceutical biodetection and TOC application support for the life science industry. Con 20 años de experiencia trabajando en y con laboratorios de control de calidad farmacéuticos, Brian ha supervisado y apoyado pruebas de alto volumen durante el proceso y productos terminados. Después de haber ocupado cargos anteriores en Wyeth y Lonza, y con nueve años de experiencia en el apoyo a la línea de productos Sievers como parte de GE Analytical Instruments, SUEZ y ahora Veolia, Brian tiene una amplia experiencia en instrumentos y software de detección de endotoxinas, incluida la instalación, la calificación y la capacitación. Brian holds a Bachelor of Science degree in Biological Sciences from York College of Pennsylvania.
Hayden Skalski: Hayden Skalski is the Life Sciences Product Application Specialist for Veolia, specializing in bacterial endotoxins testing (BET). Hayden tiene más de 10 años de experiencia en la industria farmacéutica y en microbiología de control de calidad, y ha realizado presentaciones sobre numerosos temas relacionados con las pruebas de endotoxinas. Anteriormente, Hayden ocupó cargos en Charles River Laboratories, Regeneron y Novartis, donde validó y ejecutó protocolos de desarrollo de métodos para pruebas de endotoxinas, brindó asistencia al cliente, resolvió problemas y brindó soporte para pruebas de productos de alto volumen. Hayden tiene una licenciatura en Biología de la Universidad de Albany (SUNY). Kelly Smith es bióloga principal sénior en la Organización Global de Control de Calidad Analítica de Eli Lilly and Company. He is a bacterial endotoxins subject matter expert with over 25 years of industry experience and has a B.S. in chemistry from Butler University.
Kelly Smith: Kelly Smith is a Senior Principal Biologist in the Eli Lilly and Company global Analytical Quality Control Organization. He is a bacterial endotoxins subject matter expert with over 25 years of industry experience and has a B.S. in chemistry from Butler University.

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