TOC Archives - Chemetrix

How to Get Consistent, Defensible Cleaning Validation Results with the Veolia Sievers M9

Aden May — Tue, 07 Apr 2026 13:23:54 +0000

The batch is ready. The vessel looks clean. But the documentation is not done, the QC queue is backed up and the equipment has been sitting idle waiting on analytical results.

This is the real cost of a slow or uncertain cleaning validation programme. Not the cost of the instrument. Not the complexity of the method. The cost is measured in hours of lost production, delayed releases and the quiet anxiety of knowing that if an inspector walked in right now, your data trail would not tell a clear and convincing story.

Total organic carbon (TOC) analysis exists precisely to eliminate that anxiety. When implemented correctly, it is one of the fastest, most regulator-friendly, and most operationally practical cleaning verification methods available. This article explains why so many labs are not using it that way and what it takes to change that.

What does a failed clean actually cost?

Most cleaning validation conversations start with the method. They should start with the consequence. A single failed clean in a pharmaceutical or food manufacturing facility does not just mean re-cleaning the vessel. It means halting production, quarantining potentially affected batches, initiating a deviation investigation, documenting the root cause, re-validating the cleaning cycle and demonstrating to QA that it will not happen again. In a worst-case scenario, that is days of downtime on a critical piece of manufacturing equipment.

The Chemetrix team has seen this play out in facilities relying on product-specific methods like HPLC for cleaning verification. When an unknown degradant or cleaning agent residue slips through undetected, the specific method offers no warning. TOC does. Because it measures the total organic carbon in a rinse or swab sample, it catches APIs, degradants, excipients and cleaning agents in a single analysis. There is no invisible contamination with a properly implemented TOC method.

The three most common operational pain points the Chemetrix team identifies in cleaning validation programmes are:

Poor worst-case selection. Labs test the wrong compound or the wrong surface area, which means their validation does not reflect real-world cleaning challenges.
Weak limit translation. There is a well-defined ppm requirement on paper, but nobody has converted it into an actionable TOC concentration limit for the instrument.
Inconsistent sampling. Swab technique varies between analysts, water baseline is not controlled and grab samples represent a single timepoint rather than a continuous view of the cleaning cycle.

These are workflow problems. Not instrument problems.

Why is TOC considered the gold standard for cleaning validation?

TOC analysis works by oxidising all organic residues in a sample and measuring the carbon dioxide produced. The result is a single, quantitative carbon concentration value that tells you, objectively, how much organic material remains on the equipment surface or in the final rinse.

This matters enormously in a regulated environment because it removes operator subjectivity from the result. There is no peak integration to argue about, no ghost peaks to investigate and no ambiguity about whether a signal is real or an artefact. The FDA has issued numerous warning letters specifically for HPLC data integrity failures, including failure to integrate peaks and inadequate investigation of unknown peaks. These problems are structurally unavoidable in product-specific methods because cleaning processes generate degradants and unexpected compounds that the specific method was never designed to detect.

TOC does not have this problem. It detects everything organic. That is not a liability. That is a feature. The regulatory acceptance of TOC for cleaning validation is well established. The US Pharmacopoeia, the US Food and Drug Administration and the European Medicines Agency all recognise TOC as an appropriate and compliant method for demonstrating equipment cleanliness. The FDA’s 2011 process validation guidance is particularly significant: the traditional practice of measuring a single API with a specific method is no longer considered compliant with FDA best practice, because it does not provide the process understanding the life cycle approach requires. TOC, as a non-specific method, measures both product-related and process-related residues as a function of carbon content, making it compliant with that guidance and giving a comprehensive view of cleanliness at every phase of the validation life cycle.

When sensitivity becomes a concern, it is worth reframing the question:

A TOC analyser is not too sensitive. It is appropriately sensitive. Sensitivity is exactly what guarantees that equipment is genuinely clean, not just clea

n enough to pass a method that was not looking for everything.

Is TOC actually cheaper than HPLC for cleaning validation?

The short answer is yes – in most cases, TOC is more cost-effective than HPLC, often delivering noticeable savings within the first year of implementation.

Here is what a realistic comparison looks like across the two approaches:

HPLC for cleaning validation requires a separate, validated method for each product. Method development is time-consuming and assumes that all potential interferents are fully understood. It cannot detect degradants or cleaning agent residues that fall outside the target compound. Laboratory workflow typically means grab samples are transported to the QC lab, queued for analysis and results returned hours later. Equipment sits idle during this time.

TOC for cleaning validation requires a single method that covers APIs, excipients, degradants and cleaning agents simultaneously. The Sievers M9 delivers results in two minutes in standard mode, or four seconds with the optional Turbo mode. The M9 Portable model can be taken directly to the manufacturing floor, samples can be analysed almost immediately after collection and equipment can be released faster.

The economic gains compound over time. Fewer out-of-specification investigations due to environmental or transcription errors, faster analyst throughput, reduced re-testing and the elimination of mobile phase preparation all contribute to a meaningfully lower total cost of running a cleaning validation programme.

Chemetrix Insight: “TOC almost always reduces total validation costs within the first year by accelerating batch release and reducing the frequency of re-testing. The instrument cost is recovered faster than most labs expect.”

How do you troubleshoot a TOC cleaning validation workflow that is not performing?

When TOC results are inconsistent or a cleaning validation programme is not delivering the confidence it should, the problem is almost never the analyser. Here is the hierarchy of where to look first.

Step 1: Check the water baseline. The carbon contribution of the rinse water itself must be established and controlled. If the water baseline is elevated or variable, every subsequent result will be unreliable. Low-TOC water and appropriate Sievers certified vials are the foundation of reproducible results.

Step 2: Review the swab technique. Analyst-to-analyst variability in swabbing is one of the most common sources of inconsistency in cleaning validation data. In published validation data using the Sievers M9, two different analysts achieved recovery values of 100% to 105.8% with RSD values below 2.1% for the same CIP-100 cleaning agent at multiple concentration levels, demonstrating that a well-standardised method is highly reproducible across operators. If your res

ults do not look like this, the method has not been standardised, not the instrument.

Step 3: Confirm the worst-case compound is correctly identified. Many facilities test the easiest-to-detect compound rather than the hardest-to-clean one. Worst-case selection should be based on solubility, toxicity and difficulty of removal, not analytical convenience.

Step 4: Verify the limit is correctly translated. A product limit expressed in ppm of compound is not directly equivalent to a TOC limit. The conversion requires multiplying by the percentage carbon in the chemical formula of the compound. For example, if a specific API limit is 10 ppm and the percentage carbon is 50%, the TOC limit is 5 ppm. This step is frequently skipped or done incorrectly.

Step 5: Consider the deployment. If equipment turnaround is the primary constraint, laboratory-based grab sample analysis may simply not be fast enough. At-line analysis with the M9 Portable or online analysis with the M9 On-Line can eliminate the QC queue entirely and enable real-time equipment release.

Practical resources:

Veolia Application Note: Validating the TOC Method for Cleaning Validation Applications in the Pharmaceutical Industry
Veolia Fact Sheet: Top 5 Secrets to a Successful Cleaning Validation Program
Veolia eBook: Total Organic Carbon for Cleaning Validation Programs

📌 Contact Chemetrix to request a workflow review of your current cleaning validation programme.

What makes the Veolia Sievers M9 the right instrument for pharmaceutical cleaning validation?

The Sievers M9 was not designed for a research scientist with unlimited time. It was designed for the QC technician who needs to verify that a vessel is clean, release the equipment and get back to supporting production. That distinction matters.

The Sievers Membrane Conductometric Detection method is what sets the M9 apart technically. Unlike instruments that use non-dispersive infrared (NDIR) detection, the Sievers gas-permeable membrane selectively passes only the CO₂ produced from the oxidation of organics. Acids, bases and halogenated compounds, which are frequently present in pharmaceutical cleaning processes, are prevented from interfering with the measurement. This delivers selectivity and precision in exactly the sample matrices where cleaning validation is performed.

The M9 comes in three configurations to match any deployment need:

M9 Laboratory: For QC labs running high volumes of rinse and swab samples, with optional Autosampler for 24-plus hours of unattended analysis
M9 On-Line: Attached directly to a CIP skid for continuous real-time monitoring and automated equipment release without any manual sampling
M9 Portable: Lightweight and IP-21 rated for at-line use on the manufacturing floor, supporting both rinse and swab samples with optional Turbo mode

Across all three configurations, the M9 delivers a measurement range of 0.03 ppb to 50 ppm with precision below 1% RSD and accuracy of plus or minus 2% or plus or minus 0.5 ppb, whichever is greater. Calibration is typically stable for 12 months. Maintenance requires just a few hours per year. The instrument comes pre-calibrated from the factory and can be prepared for analysis in under one hour.

For regulated environments, the optional DataGuard software provides full 21 CFR Part 11 and Annex 11 compliance, with a secured audit trail, user-level access controls and data that cannot be modified or deleted. The M9 also simultaneously reports TOC, inorganic carbon and conductivity from a single sample, giving three discrete data points that can be used together to identify root cause, optimise cleaning cycles and support OOS investigations.

Practical resources:

Veolia Application Note: Validating the TOC Method for Cleaning Validation Applications in the Pharmaceutical Industry
Veolia Fact Sheet: Top 5 Secrets to a Successful Cleaning Validation Program
Veolia eBook: Total Organic Carbon for Cleaning Validation Programs

📌 Contact Chemetrix to request a workflow review of your current cleaning validation programme.

Stop blaming the instrument and fix the workflow

The most common story Chemetrix hears is some version of this: “We tried TOC. It did not work for us.” After closer investigation, the story is almost always the same. The water baseline was not controlled. The worst-case compound had not been properly identified. The limit had not been correctly translated from ppm of compound to a TOC concentration. The sampling was inconsistent between analysts.

The instrument was fine. The workflow was not.

Chemetrix does not just supply a Sievers M9 and move on. The partnership Chemetrix offers is built around making sure the workflow is right before the instrument is even switched on, and that the team running it has the knowledge to trust the results it produces.

This means three specific things in practice:

Worst-Case Selection Support: Helping your team identify which compound, which equipment surface and which cleaning cycle represents the genuine worst case for your process, so your validation is defensible under inspection.
Limit Translation: Converting your existing acceptance criteria into actionable TOC concentration limits, accounting for the percentage carbon in the chemical formula and the sampling method used.
Sampling Standardisation: Establishing consistent swab technique, water baseline controls and vial selection across your team so that analyst-to-analyst variability is eliminated as a source of OOS investigations.

When results are consistent, compliance follows. That is not a slogan. It is the operating principle of a cleaning validation programme that works.

Conclusion

Cleaning validation does not have to be the bottleneck it has become in many facilities. The science is straightforward. The regulatory acceptance is well established. The instrument is reliable, automated and designed for QC technicians rather than research scientists.

The three things to take away from this article:

TOC catches what specific methods miss. APIs, degradants, excipients and cleaning agents are all detected in a single analysis, making it inherently more comprehensive than HPLC for cleaning verification.
Most TOC problems are sampling and workflow problems. Controlling the water baseline, standardising swab technique and correctly translating limits will resolve the vast majority of analytical inconsistencies.
The Sievers M9 is built for production environments. With two-minute analysis time, optional Turbo mode at four seconds, three simultaneous data outputs and 21 CFR Part 11 compliance, it is designed to release equipment and get out of the way.

The Sievers M9 delivers consistent, defensible proof that cleaning works. Chemetrix makes sure your workflow does too.

Ready to stop guessing and start releasing?

📩 Contact the Chemetrix team to book a cleaning validation workflow audit or arrange a Sievers M9 demonstration: chemetrix.co.za

Illuminating Insight: Where Light Meets Industry

Francois — Tue, 28 Oct 2025 15:16:43 +0000

Step into a world where precision, performance, and innovation converge.
The Chemetrix Industrial & Environmental Spectroscopy Roadshow, in partnership with Agilent Technologies and Veolia, brings together analytical excellence and industrial insight to explore how light – in all its forms – is transforming the way we measure, monitor, and protect our world.

Join leading experts for an illuminating day of discussions and discovery in Atomic Spectroscopy and Total Organic Carbon (TOC) analysis. Learn how these technologies are driving smarter, more sustainable decisions across industries – from environmental testing to industrial process control.

Agenda

Veolia Sievers TOC Analyzers for Industrial & Environmental Applications

Part 1 – Clean Water:

Introduction to the Sievers I&E Product Portfolio
M-Series Technology
Condensate & Boiler Feed Water Applications
Drinking Water & Reuse Applications

Part 2 – Contaminated Water:

InnovOx Technology
Industrial Water Applications
Food & Beverage Applications
Desalination & Brine Applications

Agilent Atomic Spectroscopy Solutions for Industrial & Environmental Applications

Part 1:

Agilent Atomic Spectroscopy Portfolio Overview
Analysis of Water Samples using Agilent ICP-MS Systems
Overcoming High-Matrix Sample Challenges through Optimized ICP Methods

Part 2:

Unlocking Mining, Food & Environmental Applications with Agilent ICP-OES 5800/5900
Choosing Between Single-Quad ICP-MS and Triple-Quad ICP-MS/MS
Coupling HPLC to ICP-MS for Speciation Applications

Chemetrix Consumables & Sample Preparation

New consumable products to optimise performance and reduce downtime
Practical guidance on sample preparation workflows

Why Attend?

Gain insight into real-world industrial and environmental applications.
Learn from industry and technical experts on how to enhance precision, productivity, and sustainability in your lab.
Network with fellow professionals shaping the future of analytical science.

Spaces are limited

Register now for the event now!

Smarter Endotoxin Testing: Reducing Reagent Use Without Compromising Accuracy

Francois — Wed, 16 Jul 2025 09:36:24 +0000

In the realm of pharmaceutical and medical device manufacturing, ensuring product safety is paramount. Bacterial Endotoxin Testing (BET) plays a crucial role in this process, traditionally relying on significant volumes of Limulus Amebocyte Lysate (LAL) derived from horseshoe crabs. However, advancements in technology are paving the way for more efficient and sustainable testing methods.

Navigating the complexities of traditional BET

Traditional BET methods, such as the gel clot and 96-well plate assays, have been the standard for decades. While effective, these techniques often involve substantial volumes of LAL, raising concerns about sustainability and cost. Moreover, the manual nature of these assays can lead to increased labour, potential for human error, and challenges in maintaining compliance with stringent regulatory standards.

The need for meticulous documentation and validation further complicates the process, making it both time-consuming and resource-intensive.

📚 Download the 1:1 Sample to Lysate Ratio application note and discover why it is crucial to show equivalency across platforms in bacterial endotoxins testing.

Embracing innovation

The Sievers Eclipse Bacterial Endotoxins Testing (BET) Platform emerges as a transformative solution addressing the limitations of traditional BET methods. Leveraging precise microfluidic liquid handling, the Eclipse platform automates kinetic chromogenic assays, significantly reducing manual intervention.

This innovation not only decreases assay setup time by up to 85% but also reduces LAL reagent consumption by up to 90%, promoting sustainability.

Furthermore, the platform fully complies with harmonised pharmacopeial requirements, including USP <85>, EP 2.6.14, and JP 4.01, ensuring data integrity and regulatory adherence. By simplifying workflows and enhancing precision, the Eclipse platform represents a significant advancement in endotoxin testing.

🖥️ Watch the Simple Steps to Get Started with the Sievers Eclipse BET Platform webinar and learn how to easily set up the Sievers Eclipse Bacterial Endotoxins Testing (BET) Platform, prepare your microplate, and start running assays.

Enhancing efficiency with Chemetrix’s support

Chemetrix, as a trusted partner in laboratory solutions, offers comprehensive support for integrating the Sievers Eclipse BET Platform into your operations. Our services include installation and validation assistance, user training, and ongoing technical support to maximise the platform’s capabilities. With Chemetrix’s expertise, laboratories can confidently transition to more efficient and sustainable BET practices.

Achieving sustainability goals

The Sievers Eclipse BET Platform not only enhances operational efficiency but also contributes to environmental sustainability. By significantly reducing LAL usage, laboratories can lower their environmental impact and operational costs. Adopting the Eclipse platform reflects a commitment to ethical and environmentally conscious operations, aligning laboratory practices with broader sustainability objectives.

🖥️ Watch the 3 Ways to Simplify Endotoxin Testing webinar and explore how the Sievers Eclipse BET Platform can bring efficiency, ease, and simplicity to your lab without sacrificing compliance and quality control.

Realising the benefits of modern BET practices

Laboratories that have adopted the Sievers Eclipse BET Platform report notable improvements, including increased throughput, enhanced data integrity, and regulatory confidence. These benefits underscore the value of modernising BET practices to meet current and future demands.

📚 Download the How Different Endotoxin Testing Platforms Work infographic for a visual summary of kinetic chromogenic testing systems.

Partner with Chemetrix for advanced BET solutions

Elevate your laboratory’s endotoxin testing capabilities by embracing the Sievers Eclipse BET Platform. Chemetrix is ready to support your transition with expert guidance, comprehensive services, and ongoing support.

Contact Chemetrix today to learn how we can assist in enhancing your laboratory’s efficiency, sustainability, and compliance through innovative BET solutions.

The Benefits of Following the Carbon in your Process Water

Francois — Tue, 03 Sep 2024 13:00:27 +0000

It’s well known that around 70% of the Earth’s surface is covered in water. It’s our most precious natural resource and great efforts have been made globally to protect the finite supply of water for the planet’s inhabitants. Growing population, climate change, and industrial contamination are some of the issues that cause water stress and impact water quality. This is why analytical testing to ensure water quality and safety is essential for health and the ecosystem.

There’s no denying that sustainability is a big topic for water management and resource conservation. As industries continue to prioritise eco-friendly practices, carbon monitoring will play a crucial role in achieving these goals, demonstrating a commitment to both innovation and environmental responsibility. But what does it mean to follow the carbon, and how does it benefit your operations?

What it means to follow the carbon

Following the carbon throughout your processes allows you to monitor processes or quality and pinpoint issues as they come about. Starting from the source water to the water that is used in the plant as utility and process water, and ultimately wastewater that is purified and discharged back into the environment, carbon monitoring can track the changing levels as the water moves throughout the facility and monitor levels if something goes awry. By monitoring carbon levels at each stage, facilities can gain valuable insights into their processes and quality control, enabling them to pinpoint issues as they arise and take timely corrective actions.

Download the eBook on the Power of Organics Monitoring >

Some of the benefits of following the carbon include:

Process optimisation – Facilities can improve the efficiency of the treatment process, reduce chemical use, and lower energy consumption.

Quality control – Continuous carbon monitoring helps maintain consistent water quality, which is critical for processes that require precise conditions, such as pharmaceutical production and food processing.

Regulatory compliance – Accurate carbon tracking provides the necessary data for regulatory reporting, demonstrating a facility’s commitment to environmental stewardship and compliance.

Let’s talk about TOC

Total Organic Carbon is a common measurement to gauge the amount of carbon-based compounds in water. TOC analysis aims to help corporations and municipalities reduce and optimise water use, comply with permit and regulatory requirements, and demonstrate safety and quality standards while maintaining asset reliability.

It provides reliable data and is written in many regulatory guidelines around the world and across various industries.

TOC and conductivity analysis aids in detecting chemical impurities in pharmaceutical-grade water systems and process equipment. Using TOC to understand the comprehensive cleanliness of water and equipment allows manufacturers to consistently deliver safe, high-quality drug products. Many TOC technologies work by oxidising organic molecules using UV or chemical oxidation and measuring the resulting CO2.

Watch our webinar on TOC and Conductivity Analysis: Back to Basics >

Water soluble compounds can be analysed using TOC analysis with little to no method variation. Compounds that do not readily solubilise in water can still be detected using small adjustments such as: agitation, pH, or temperature. With Sievers TOC Analyzers, consumables, and expertise from Veolia, you can be confident your method development will go smoothly.

The Veolia TOC-R3 Online Total Organic Carbon (TOC) and Total Nitrogen (TN) Analyzer is designed to solve critical industrial and environmental water challenges. From source water contamination and condensate leaks to wastewater optimisation and discharge, the TOC-R3 is a peace of mind analytical tool that provides responsiveness and repeatability.

Veolia TOC-R3 Online TOC Analyzer

Following the carbon in process water is an essential practice for modern industrial facilities. By systematically monitoring carbon levels, companies can protect their assets, optimise processes, maintain high-quality standards, and ensure regulatory compliance. This not only contributes to operational efficiency and cost savings but also supports environmental sustainability. As industries continue to prioritise eco-friendly practices, carbon monitoring will play a crucial role in achieving these goals, demonstrating a commitment to both innovation and environmental responsibility.

EnviroTech – Transforming Wastewater Treatment with TOC Monitoring

Francois — Tue, 27 Jul 2021 19:14:27 +0000

Organic load is one of the most important parameters for discharge control of municipal and industrial wastewater. Permissible limits are guided through regulations and must be monitored accordingly. However, further opportunity to optimize plant performance exists by monitoring organic loading in upstream treatment processes.

The use of on-line controls allows limit values to be adhered to, products to be saved, and plants to be protected against unforeseen events. Total Organic Carbon (TOC) is the most suitable parameter to measure organic load. The use of TOC analysis offers shorter measuring cycles without hazardous waste and is better suited for on-line analysis compared to conventional methods such as COD or BOD.

What you’ll learn

Differences between TOC, BOD and COD, and why TOC is more suitable for on-line control
Differences in TOC technologies
How TOC can help optimize your plant
Examples and case studies of how TOC can be utilized

Register Here >

Driving Quality with Real-time TOC Data in Food & Beverage

Francois — Tue, 27 Jul 2021 19:00:13 +0000

The Food and Beverage industry is constantly faced with demands to meet product quality and production goals. Some of the challenges to this include product recalls, equipment maintenance, and meeting compliance, all of which may be impacted by water quality. Product contamination tops the list of reasons why product recalls occur and errors during the process can be very costly. Water quality monitoring helps mitigate the risks of contamination, product loss, and costly fines. Join this webinar to find out how monitoring for organics by specifically using Total Organic Carbon (TOC) can help your F&B facility achieve production and quality goals.

What You’ll Learn

What is TOC?
Areas that can benefit from TOC monitoring in your Food & Beverage facility
TOC compared to other monitoring methods
TOC monitoring solutions

Speaker

Melvyn Lam, APAC Application Specialist for the Sievers* instrument product line by SUEZ

Melvyn Lam is the APAC Applications Specialist for SUEZ. He has 12 years’ experience in engineering and offering application support for industrial and environmental markets. Most recently he served as the APAC Application Specialist supporting business growth in Pharmaceutical and Industrial markets for a cartridge filter device company. Melvyn holds a Bachelor of Chemical Engineering and a Masters in Science, Management of Technology.

Register Here >

Cleaning Validation – A Beginner’s Guide to Increasing Efficiency with TOC

Francois — Tue, 27 Jul 2021 18:51:55 +0000

Join our webinar which will guide you through efficiency gains with TOC for cleaning validation. We call it a ‘beginner’s guide’, but this webinar will benefit long-time TOC users as well as those new to using TOC for cleaning validation. We will cover step-by-step the ‘what, why, and how’ for gaining efficiency and getting the … Continue reading

TOC and Conductivity Analysis: Back to Basics

Francois — Tue, 27 Jul 2021 18:30:12 +0000

This webinar is designed to get back to basics as a refresher for seasoned users or as an introduction for those new to total organic carbon (TOC) and conductivity analysis, USP <643>, and USP <645>.

Join this interactive discussion to learn practical tips for day-to-day use of TOC for compendial water testing and cleaning validation.Total organic carbon (TOC) and conductivity analysis can be used in a variety of applications and are very useful in assessing cleanliness, water quality, and process performance.

It is compulsory for manufactures to abide by the regulations for TOC and conductivity, however, not all end users understand how the technology works and why it is important. In this webinar we’ll cover the basics and provide quick tips for success from the user’s perspective.

This webinar will cover:

Regulations: Understanding USP <643> Total Organic Carbon, USP <645> Conductivity, data integrity, and regulatory expectations for cleaning validation
Basic principles of TOC and conductivity: Overview of Sievers technology and applications
Data analysis: What story are the data telling?
Best practices, troubleshooting, and quick tips
Data integrity and validation

Who should attend:

QA & QC personnel
Validation personnel
Operations personnel