Regulatory compliance Archives - Chemetrix https://chemetrix.co.za/tag/regulatory-compliance/ Powerful Partnership, Inspiring Insights Tue, 07 Apr 2026 13:23:54 +0000 en-US hourly 1 https://wordpress.org/?v=6.3.8 How to Get Consistent, Defensible Cleaning Validation Results with the Veolia Sievers M9 https://chemetrix.co.za/how-to-get-consistent-defensible-cleaning-validation-results-with-the-veolia-sievers-m9/ https://chemetrix.co.za/how-to-get-consistent-defensible-cleaning-validation-results-with-the-veolia-sievers-m9/#respond Tue, 07 Apr 2026 13:23:54 +0000 https://chemetrix.co.za/?p=7356 Continue reading "How to Get Consistent, Defensible Cleaning Validation Results with the Veolia Sievers M9"]]> 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

]]> https://chemetrix.co.za/how-to-get-consistent-defensible-cleaning-validation-results-with-the-veolia-sievers-m9/feed/ 0 Ensuring Food Safety with Mass Spectrometry https://chemetrix.co.za/ensuring-food-safety-with-mass-spectrometry/ https://chemetrix.co.za/ensuring-food-safety-with-mass-spectrometry/#respond Mon, 17 Mar 2025 08:00:49 +0000 https://chemetrix.co.za/?p=6737 Continue reading "Ensuring Food Safety with Mass Spectrometry"]]> In an interconnected world where food production and trade span continents, ensuring the safety and quality of food products has become a critical priority. Rising consumer expectations and increasingly stringent regulatory standards mean stakeholders in the food industry must navigate a complex web of challenges. From detecting contaminants to meeting compliance requirements, the stakes are high. This is where cutting-edge technologies like mass spectrometry are stepping in to revolutionise food safety testing, delivering unmatched precision, efficiency, and reliability.

 

The growing importance of Food Safety

Food safety is non-negotiable. Defined by the World Health Organization (WHO) as the prevention of hazards – both chronic and acute – that can harm consumer health, it forms the backbone of a trustworthy food supply chain. Hazards may include microbial contamination, pesticide residues, heavy metals, and even naturally occurring toxins, all of which can pose serious risks if left unchecked.

Food quality, while often considered alongside safety, addresses different concerns. It encompasses attributes such as flavour, texture, appearance, and even the origin of a product. While safety ensures a product is fit for consumption, quality determines its value and appeal to consumers.

For food producers, striking a balance between these two aspects is essential to building trust and maintaining competitiveness.

 

Why Mass Spectrometry?

Mass spectrometry has become a cornerstone of modern food safety testing, thanks to its unparalleled sensitivity, accuracy, and versatility. Unlike traditional methods, which may require separate tests for different contaminants, mass spectrometry can detect and quantify multiple analytes in a single run. This capability significantly enhances efficiency and reduces the time required for analysis – a critical advantage for laboratories handling high sample volumes.

 

Key Advantages of Mass Spectrometry in Food Safety

Unmatched sensitivity and precision

Mass spectrometry can detect contaminants at trace levels, often in parts per billion (ppb) or even parts per trillion (ppt). This is vital as regulatory agencies worldwide demand more stringent detection limits to protect public health.

Multi-analyte detection

With mass spectrometry, laboratories can analyse multiple contaminants simultaneously, including pesticides, heavy metals, mycotoxins, and allergens. This not only improves throughput but also reduces the cost and complexity of testing.

Simplified sample preparation

Advanced mass spectrometry systems streamline sample preparation, reducing the likelihood of human error while speeding up the testing process.

Adaptability across food matrices

From solid foods like grains and meats to liquids like milk and juices, mass spectrometry can handle diverse food matrices, making it a versatile solution for the food industry.

 

📚 Download the Food Safety Applications in Mass Spectrometry primer for a practical reference for applying current developments in Agilent MS technologies to food analysis: https://chemetrix.co.za/wp-content/uploads/2024/12/5989-1270EN-AGI_74_combined.pdf

 

Transforming Food Safety Testing

One of the most significant developments in mass spectrometry is the rise of inductively coupled plasma mass spectrometry (ICP-MS). Historically viewed as complex and challenging to operate, ICP-MS has undergone a transformation. Modern instruments now feature user-friendly interfaces, automated optimisation, and built-in diagnostic tools, making them accessible to labs of all sizes.

ICP-MS is particularly valuable for detecting heavy metals such as lead, cadmium, and mercury, which can have severe health consequences even at low concentrations. The technique’s sensitivity and specificity ensure that contaminants are accurately identified and quantified, enabling producers to meet regulatory requirements with confidence.

Another breakthrough is the integration of liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). These methods are widely used for detecting pesticide residues and volatile organic compounds in food products. The combination of chromatography and mass spectrometry allows for the separation and precise identification of compounds within complex mixtures, ensuring reliable results.

Agilent 7000D Triple Quadrupole GC-MSMS
Agilent 6495C LC/MSMS

📚 Download the Improving Food Safety Analysis with LC/Q-TOF compendium of application notes and explore analysis of pesticides, nontargeted screening approaches for contaminants, and food authenticity testing: https://chemetrix.co.za/wp-content/uploads/2024/12/Improving_Food_Safety_Analysis-with-LC_Q-TOF-Feb2020.pdf

 

Addressing the challenges of a globalised food supply chain

In a globalised food economy, the complexity of supply chains adds another layer of risk. Ingredients sourced from diverse regions can introduce contaminants at various stages, making robust testing protocols indispensable. Additionally, the transportation and storage of food products can create opportunities for microbial growth or chemical alterations.

Regulatory bodies worldwide, such as the European Food Safety Authority (EFSA) and the United States Food and Drug Administration (FDA), have responded by tightening standards and lowering acceptable thresholds for contaminants. As a result, food manufacturers must adopt advanced technologies to stay ahead of compliance requirements.

Mass spectrometry provides the tools needed to address these challenges. Offering rapid, reliable testing, enables stakeholders to identify potential issues early in the supply chain. For example, a shipment of imported spices can be tested for pesticide residues before distribution, preventing contaminated products from reaching consumers.

Moreover, mass spectrometry supports traceability – a key component of modern food safety systems. By linking test results to specific batches or production lots, producers can quickly identify and recall affected products in the event of a safety breach. This level of accountability is essential for maintaining consumer trust and avoiding costly disruptions.

📚 Download the Multi-Residue Pesticide Analysis in Food Matrices poster to see how the screening and quantitation of 250 pesticides was done using the Agilent Ultivo Triple Quad: https://chemetrix.co.za/wp-content/uploads/2024/12/Multi-Residue_Pesticide_Analysis-_Food_Matrices_Ultivo_AOAC_2017_PW044.pdf

 

Chemetrix: Your partner in Food Safety

Chemetrix is at the forefront of delivering advanced mass spectrometry solutions tailored to the needs of the food industry. With a deep understanding of the unique challenges faced by producers, regulatory agencies, and testing laboratories, Chemetrix provides comprehensive support to ensure optimal performance and compliance.

Why choose Chemetrix?

  • Cutting-Edge Instrumentation: Chemetrix offers state-of-the-art mass spectrometry systems, including ICP-MS, LC-MS, and GC-MS, designed for precision and efficiency.
  • Expert Guidance: From installation to training and ongoing support, Chemetrix’s team of experts ensures that clients can fully leverage their technology investments.
  • Tailored Solutions: Recognising that every client has unique requirements, Chemetrix works closely with stakeholders to develop customised workflows that meet their specific needs.

By partnering with Chemetrix, food producers and testing labs gain access to the tools and expertise needed to navigate the complexities of modern food safety testing with confidence.

 

The Future of Food Safety

As food systems evolve, so too must the methods used to ensure their safety. Mass spectrometry represents a critical step forward, offering the precision, speed, and adaptability needed to meet the challenges of an increasingly interconnected world.

For the food industry, adopting advanced testing technologies is not just about compliance – it’s about safeguarding public health, protecting brand reputation, and building trust with consumers. With partners like Chemetrix leading the way, the future of food safety is brighter, more secure, and more innovative than ever.

]]> https://chemetrix.co.za/ensuring-food-safety-with-mass-spectrometry/feed/ 0 The Importance of Biopharma Analytical Testing https://chemetrix.co.za/the-importance-of-biopharma-analytical-testing/ https://chemetrix.co.za/the-importance-of-biopharma-analytical-testing/#respond Mon, 03 Feb 2025 08:15:32 +0000 https://chemetrix.co.za/?p=6727 Continue reading "The Importance of Biopharma Analytical Testing"]]> In the world of biopharmaceuticals, precision and safety are non-negotiable. As companies work to develop advanced therapies and biologics, the role of analytical testing becomes ever more critical. Analytical testing serves as the backbone of biopharma development, ensuring that every product released to the market meets stringent regulatory standards while maintaining the highest safety and efficacy levels. Chemetrix supports this vital process by equipping laboratories with state-of-the-art technologies to optimise testing workflows and ensure regulatory compliance.

 

Why Analytical Testing Matters in Biopharma

Biopharmaceutical products, including monoclonal antibodies, cell and gene therapies, and vaccines, are inherently complex. Unlike traditional small-molecule drugs, these products are often derived from living cells, making them highly sensitive to variations in manufacturing and storage conditions.

Analytical testing ensures the quality, purity, potency, and stability of biopharmaceuticals throughout their lifecycle, from early development to final product release.

Without rigorous testing, even minor inconsistencies in a product can lead to reduced efficacy, compromised safety, or regulatory non-compliance. By employing advanced analytical methods, biopharma companies can identify impurities, confirm molecular structures, and monitor critical quality attributes (CQAs) that are essential for maintaining product integrity.

📚 Download The Journey to Biopharma infographic to discover streamlined automation and cutting-edge analytics >

 

Key Phases of Analytical Testing

Early development

During the early stages of biopharma development, testing focuses on characterising the biological product and defining CQAs. Techniques such as mass spectrometry, high-performance liquid chromatography (HPLC), and spectroscopy play a central role in these analyses. These tools help determine factors like molecular weight, structural integrity, and glycosylation patterns.

Process development

As manufacturing processes are developed, analytical testing ensures consistency and scalability. Process-related impurities, such as host cell proteins or residual solvents, must be identified and quantified. Additionally, methods like capillary electrophoresis and liquid chromatography-mass spectrometry (LC-MS) are employed to optimise purification steps and ensure process robustness.

Final product release

Before a product reaches the market, it undergoes comprehensive testing to confirm that it meets regulatory specifications. This includes assays for potency, sterility, endotoxin levels, and stability. Modern analytical platforms, such as multi-mode plate readers and automated systems, provide the throughput and accuracy needed for these critical assessments.

 

Trends in Analytical Testing for Biopharma

Emergence of advanced techniques

The biopharma industry is increasingly adopting technologies like LC-MS and next-generation sequencing (NGS) to enhance analytical capabilities. These methods allow for greater sensitivity and specificity, enabling researchers to detect low-level impurities and subtle molecular changes that could impact product performance.

Adoption of automation and AI

Automation is transforming analytical testing, reducing human error and increasing throughput. AI-driven software is also being integrated into testing workflows, enabling predictive analytics and more efficient data interpretation.

Focus on emerging therapies

The rise of cell and gene therapies has introduced new challenges for analytical testing. These therapies require novel analytical approaches to address their unique complexities, such as the characterisation of viral vectors and the assessment of genome editing outcomes.

Regulatory compliance and data integrity

With stringent guidelines from organisations like the FDA and EMA, ensuring data integrity has become a top priority. Advanced software systems with audit trails and robust data management capabilities are increasingly essential in biopharma testing.

 

Driving excellence in Analytical Testing

Chemetrix is at the forefront of supporting biopharma companies with advanced analytical solutions. By offering cutting-edge instruments and technologies, we help laboratories address the challenges of testing biologics and other complex products.

We provide access to industry-leading platforms, including HPLC systems, LC-MS, and next-generation spectroscopy tools. These technologies are designed to deliver high sensitivity and precision, ensuring that every aspect of a biopharmaceutical product is rigorously tested.

The new generation Agilent 1260 Infinity III is a robust instrument that delivers the performance, reliability, and robustness you need for the highest confidence in daily HPLC results. With the freedom to mix and match new modules with existing HPLC instrumentation, it’s possible to maximise uptime and minimise disruption while also getting on the fast track to efficiency, optimizing speed and resolution for analysis.

Agilent 1260 Infinity II

Moreover, Chemetrix offers comprehensive support services, from installation and training to ongoing maintenance and technical assistance. This ensures that labs can maximise the performance of their analytical equipment and stay ahead of industry demands.

📚 Download the Mass Spectrometry of Macromolecules Using Standard Flow LC/MS application note to discover a robust and sensitive LC/MS method using standard LC flow for the analysis of native protein analysis >

 

The importance of analytical testing in biopharma cannot be overstated. As the industry continues to evolve, the need for advanced testing methods will only grow. By leveraging state-of-the-art technologies and partnering with trusted providers like Chemetrix, biopharma companies can ensure the safety, efficacy, and quality of their products while meeting regulatory expectations. With our commitment to innovation and excellence, Chemetrix stands as a trusted ally for laboratories navigating the complexities of biopharma analytical testing.

 

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