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Resultados da pesquisa: Teste de verificação de controle positivo usando teste rápido de biocarga

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. Ela possui mais de 10 anos de experiência na indústria de testes de endotoxinas bacterianas e ocupou vários cargos em controle de qualidade, suporte técnico e gerenciamento de produtos. Antes de ingressar na Veolia, Meg foi gerente de produtos da Charles River Laboratories. Ela tem foco no cliente e gosta de resolver problemas na prática, seja para questões técnicas, assistência de ensaio ou 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. Ela tem mais de 10 anos de experiência em microbiologia abrangendo ciências da vida, ciências ambientais, instalações de tratamento de água e instrumentação analítica. Em sua função atual, ela desenvolve e implementa métodos analíticos para plataformas de teste de endotoxinas e biocarga. Anteriormente, o Irma dirigiu experimentos para o desenvolvimento de ensaios de microbiologia de diagnóstico rápido, incluindo testes de suscetibilidade a antibióticos e identificação. Ela é movida por uma filosofia enraizada na gestão ambiental e na responsabilidade pela saúde 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 obteve seu Bacharelado em Microbiologia pela Universidade do Arizona em 2016, Cort trabalhou em várias capacidades como especialista no assunto de microbiologia, com um foco particular em citometria de fluxo. Conhecido por sua abordagem prática de solução de problemas, Cort se dedica ao avanço da tecnologia de biodetecção e ao fornecimento de soluções inovadoras para a indústria de biotecnologia. 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 suas funções na indústria de instrumentação, Matt foi professor de cursos laboratoriais em microbiologia na Universidade do 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. Um dos principais colaboradores do analisador de endotoxinas Sievers Eclipse, Vincent foi responsável por projetar os padrões pré-depositados apresentados no dispositivo consumível. Sua experiência se reflete na publicação em co-autoria, "Miniaturization, Parallelization, and Automation of Endotoxin Detection by Centrifugal Microfluidics", publicada na Analytical Chemistry. Antes de sua função atual, Vincent contribuiu para os métodos analíticos para testes de vacinas contra flavivírus na Inviragen e na Takeda Vaccines, incluindo a realização de testes clínicos para a vacina contra a 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 um dos principais colaboradores do analisador de endotoxinas Sievers Eclipse, Gary foi responsável pelo desenvolvimento e validação de processos de fabricação, metodologia analítica e estabilidade do produto. Antes de ingressar na Veolia, Gary passou 20 anos na indústria biofarmacêutica com várias funções em P&D, controle de qualidade e garantia de qualidade. 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. Ela é formada em Biologia e Química pela Colorado State University-Pueblo. Anne's career has taken her through multiple sectors, beginning in water treatment before transitioning to the pharmaceutical industry.

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Visão geral das regulamentações: USP <645> "Condutividade de água"

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. Em aplicações de qualidade de água, a condutividade resulta de material iônico dissolvido. Em sistemas de água farmacêutica altamente controlados, as mudanças de condutividade geralmente indicam contaminação, embora a condutividade também sirva como um indicador da composição, química e consistência da água. 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. Juntos, esses testes de limite químico essencial determinam se há controle suficiente no sistema de purificação de água. O COT e a condutividade fornecem avaliações não específicas da qualidade da água, o que significa que não identificam espécies contaminantes específicas, mas medem classes inteiras 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 exemplo, embora os tratamentos de pré-condicionamento, como ozônio e eletrodeionização (EDI), reduzam a contaminação, eles próprios podem contribuir com contaminantes se não forem gerenciados adequadamente. 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. Eles acomodam cenários de teste on-line e off-line com considerações para determinar a adequação do contêiner de amostra. 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. É o mais simples de executar, exigindo o menor tempo por amostra. A automatização dos testes USP <645> de estágio 1 oferece economia de tempo significativa, bem como maior integridade e segurança dos dados. 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. Se a leitura for inferior a uma rede de 0,1 μS/cm por 5 minutos, a condutividade é anotada. O limite de condutividade para o Estágio 2 é 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. A temperatura da amostra é mantida em 25±1°C com a adição de cloreto de potássio. O pH é determinado com a unidade de pH mais próxima de 0,1. 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. As amostras são coletadas e testadas automaticamente enquanto os dados são registrados perfeitamente, fornecendo monitoramento contínuo. Isso se aplica apenas aos testes de Estágio 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. Essas preocupações podem ser resolvidas usando instrumentos de bancada que testam a condutividade e o carbono orgânico total (COT) simultaneamente usando o mesmo frasco de amostra. 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. Em baixos níveis de condutividade, as amostras são particularmente suscetíveis a relatórios incorretos devido aos efeitos de absorção e dessorção de CO2, que podem introduzir vieses de medição não intencionais. 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. Essas verificações adicionais não são requisitos regulamentares, mas fornecem às instalações uma confiança adicional na adequação do 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. Nossa experiência líder no setor garante que você seja apoiado com estratégias completas de validação e implantação 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 começou seu mandato na linha de produtos Sievers como parte da GE Analytical Instruments em 2011 na organização de serviço de campo e, mais tarde, foi responsável por liderar a equipe de Serviços Técnicos da América do Norte, onde supervisionou o suporte técnico, o serviço de fábrica e as operações do processo de renovação. Antes de ocupar cargos nos produtos Sievers, Tony serviu por 10 anos na Marinha dos EUA, onde supervisionou inspeções de voo e realizou inspeções de garantia de qualidade e manutenção de complexos radares eletrônicos e pacotes de comunicação. 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 tem apoiado clientes de instrumentos Sievers nos últimos seis anos com experiência em aplicações de COT e endotoxinas. Ela forneceu serviços de desenvolvimento de métodos e testes de viabilidade para fabricantes farmacêuticos e apresentou em mais de 20 conferências nacionais. Sydney holds a Bachelor of Science degree in Chemistry from the University of Northern Colorado..

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Resultados da pesquisa: validação de rCR em uma plataforma de teste de endotoxina com microfluidos em vários sorotipos de bactérias 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. Ao utilizar a tecnologia recombinante, o rCR replica toda a cascata de LAL sem depender de recursos derivados do caranguejo-ferradura, alinhando-se às metas de sustentabilidade do setor. 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. As soluções foram diluídas para atingir as respostas alvo de 0,5 a 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. Ela oferece uma ampla experiência que é vital para os clientes da ACC quando se trata de suporte técnico de testes de matrizes de amostras complexas, solução de problemas, validações de métodos, investigações e aspectos regulatórios de BET. Mais recentemente, Veronika tem estado fortemente envolvida na avaliação e implementação de tecnologias recombinantes e sua automação. 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. Ela possui mais de 10 anos de experiência na indústria de testes de endotoxinas bacterianas e ocupou vários cargos em controle de qualidade, suporte técnico e gerenciamento de produtos. Antes de ingressar na Veolia, Meg foi gerente de produtos da Charles River Laboratories. Ela tem foco no cliente e gosta de resolver problemas na prática, seja para questões técnicas, assistência de ensaio ou 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. Um dos principais colaboradores do analisador de endotoxinas Sievers Eclipse, Jake foi responsável por projetar os padrões pré-depositados apresentados no dispositivo de consumível de microfluidos. Jake foi coautor da pesquisa sobre detecção de endotoxinas com microfluidos, "Miniaturization, Parallelization, and Automation of Endotoxin Detection by Centrifugal Microfluidics", que foi publicada na Analytical Chemistry. Antes de ingressar na Veolia, Jake contribuiu para o desenvolvimento de métodos analíticos para testes de vacinas contra flavivírus nas vacinas Inviragen e Takeda, incluindo testes de ensaios clínicos para a vacina contra a dengue, Qdenga. He holds a B.S. from Colorado State University.

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Industrial and Environmental

Otimize as configurações de energia de EDI para melhorar a qualidade da água 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. O sistema opera usando campos elétricos para extrair íons através de resinas de troca e através de membranas, purificando a água e regenerando as resinas ao mesmo tempo. 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 exemplo, quando as tensões do sistema de EDI são ajustadas, pode demorar uma semana ou mais para que os níveis de contaminantes se estabilizem, durante o qual a qualidade da água do sistema pode variar de forma imprevisível. Os fabricantes passam por esses períodos de transição com monitoramento em tempo real para fazer ajustes constantes enquanto mantêm a produção e a qualidade do wafer. 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. Embora tenha sido descoberto que configurações de energia mais altas removem com mais eficiência contaminantes como boro e sílica, elas também revelaram uma desvantagem inesperada: o aumento das tensões de EDI promoveu a formação de formas iônicas de dióxido de carbono dissolvido, potencialmente levando a uma maior condutividade na 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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Dicas e truques: voltando ao básico do teste de biocarga

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. A contaminação microbiana pode levar a riscos como comprometimento da eficácia do produto, recalls dispendiosos de produtos e, o mais importante, potenciais perigos à saúde dos consumidores. Os níveis de biocarga são um importante indicador da qualidade do processo de fabricação. 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. Embora nem todos os RMM sejam criados da mesma forma, algumas tecnologias de detecção microbiana rápida se correlacionam bem com as contagens de placas tradicionais, tornando-as uma escolha ideal para fabricantes que buscam velocidade e confiabilidade. 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. Ele funciona combinando citometria de fluxo de alto rendimento com colorações de viabilidade exclusiva para fornecer resultados de biocarga quase em tempo real que se correlacionam com as contagens de placas. Operando a 8 mL/min (significativamente mais rápido que o μL/min. da citometria de fluxo tradicional), o analisador fornece resultados em menos de 45 minutos com sensibilidade abaixo de 10 células viáveis/100 mL em comparação com métodos convencionais que exigem de 2 a 7 dias. O sistema usa algoritmos sofisticados para distinguir com precisão entre partículas vivas e não vivas, permitindo que os fabricantes farmacêuticos façam a transição de controles de processo retrospectivos para controles de processo proativos. 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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Dicas e truques: voltando ao básico de carbono orgânico total e condutividade

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. O COT é essencial porque até mesmo vestígios de contaminação orgânica podem comprometer a qualidade do produto e a segurança do consumidor. O COT provém de fontes naturais (ou seja, plantas e animais) e materiais sintéticos (ou seja, produtos de limpeza, plásticos e 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 processo permite a análise sem interferência de outros 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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Dicas e truques: Voltando aos fundamentos do teste 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. Embora não sejam organismos vivos em si, elas são cruciais para a sobrevivência bacteriana e têm múltiplas funções, incluindo integridade estrutural e 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. As principais vantagens incluem uma redução de 89% nas etapas de pipetagem e tempo de configuração de apenas 5 a 10 minutos. A plataforma Eclipse usa uma placa de microfluidos para misturar amostras com reagente LAL, usando apenas 1 mL de reagente LAL — 90% menos do que os métodos convencionais — sem perder a precisão. 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. Os resultados são medidos em unidades de endotoxinas (EU), com 1 EU sendo aproximadamente igual a 1 parte por trilhão (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. A tecnologia de microfluidos também oferece aos usuários flexibilidade na escolha de reagentes, quer eles escolham o LAL tradicional ou o reagente em cascata 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

Maximizando o desempenho da caldeira com o monitoramento de COT: como o monitoramento de orgânicos protege o equipamento e a lucratividade enquanto aumenta a eficiência da caldeira

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. Seja gerando eletricidade para comunidades ou apoiando processos críticos de fabricação, esses sistemas de geração de vapor exigem água ultrapura livre de contaminantes orgânicos para operar com segurança e eficiência. 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. Com as altas temperaturas e pressões inerentes aos ciclos de água-vapor, até mesmo vestígios de compostos orgânicos podem degradar-se em ácidos orgânicos e acelerar os danos. 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. Vazamentos de glicol forçaram o desligamento de usinas de energia em várias instalações, enquanto uma grande refinaria do Texas sofreu contaminação por condensado de vapor e incrustação de caldeira que resultaram em desligamentos não planejados e perdas financeiras significativas. 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. Os vazamentos de glicol, por exemplo, não são detectados devido ao seu estado não iônico à temperatura e pressão ambientes. 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. O COT serve como uma das principais medições para indicar possíveis problemas de corrosão e integridade do sistema antes que consequências prejudiciais ocorram, algo que os métodos tradicionais de monitoramento geralmente não conseguem. O monitoramento de COT identificou com sucesso a contaminação por glicol em usinas de energia, permitindo uma manutenção proativa que evitou paradas dispendiosas. 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. Esse método de oxidação comprovado alcança mais de 99% de eficiência de oxidação, oferecendo precisão e exatidão superiores na medição de COT em toda a gama de contaminantes potenciais. Ao fornecer visibilidade em tempo real da qualidade da água da caldeira, o InnovOx ajuda a otimizar o desempenho, minimizar a manutenção não planejada e aumentar a lucratividade. 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

Principais Descobertas: Teste de Endotoxinas Bacterianas Usando Reagentes Recombinantes e Tecnologia Microfluídica Inovadora

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. Os testes de endotoxina são um excelente exemplo dessa mudança, já que as pressões regulatórias e de sustentabilidade estão transformando o cenário 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). A plataforma utiliza microfluídica e força centrípeta; permite a instalação do teste em 85% do tempo necessário para configurar uma microplaca tradicional de 96 poços; utiliza até 90% menos LAL ou rCR; e automatiza a entrega do LAL às amostras. 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. O objetivo principal foi avaliar a detecção e a recuperação de endotoxinas de ocorrência natural (NOE) e água purificada com endotoxina padrão de referência (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. Ele é especialista no assunto de endotoxinas bacterianas e lidera uma equipe com supervisão global de controle de qualidade para métodos de teste de endotoxinas, microbiologia e virologia. Jay é formado em Biologia e certificado em Estudos Ambientais pela Universidade de Indiana e tem mais de 25 anos de experiência na indústria em desenvolvimento, microbiologia de processos e laboratórios, e liderança em laboratórios de microbiologia. Jay é membro do Comitê de Especialistas em Microbiologia da United States Pharmacopoeia e é autor de um capítulo de livro e de vários artigos revisados por pares sobre endotoxinas. Accordion content 1.
Meg Provenzano: Meg Provenzano is the Global Product Manager for Sievers bio-detection instruments at Veolia. Ela possui mais de 10 anos de experiência na indústria de testes de endotoxinas bacterianas e ocupou vários cargos em controle de qualidade, suporte técnico e gerenciamento de produtos. Antes de ingressar na Veolia, Meg foi gerente de produtos da Charles River Laboratories. Ela tem um foco no cliente e gosta de resolver problemas na prática, seja para questões técnicas, assistência de ensaio ou 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. Com 20 anos de experiência trabalhando em e com laboratórios de controle de qualidade farmacêutica, Brian supervisionou e apoiou testes de produtos acabados e em processo de alto volume. Tendo ocupado cargos anteriores na Wyeth e na Lonza, e com nove anos de experiência no suporte à linha de produtos Sievers como parte da GE Analytical Instruments, SUEZ e agora Veolia, Brian tem profundo conhecimento em software e instrumentação de detecção de endotoxinas, incluindo instalação, qualificação e treinamento. 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 tem mais de 10 anos de experiência na indústria farmacêutica e em microbiologia de controle de qualidade e apresentou vários tópicos relacionados a testes de endotoxinas. Anteriormente, Hayden ocupou cargos na na Charles River Laboratories, na Regeneron e na Novartis, validando e executando protocolos de desenvolvimento de métodos para testes de endotoxinas, fornecendo suporte ao cliente, solução de problemas e suporte a testes de produtos de alto volume. Hayden é bacharel em Biologia pela Universidade de Albany (SUNY). Kelly Smith é bióloga principal sênior da organização global de controle de qualidade analítica 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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