X-ray fluorescence (XRF) spectroscopy provides many benefits over traditional elemental analysis techniques for pharmaceutical applications, including inductively coupled plasma (ICP) spectrometry. ICP techniques require highly skilled operators as well as hazardous and time-consuming sample preparation. In contrast, XRF sample preparation is much faster, less complex, and doesn’t destroy the sampled material in the process. These improvements are particularly beneficial in the scale-up context, as specialized labor as well as drug substances and formulations are in short supply. XRF analysis therefore greatly improves the efficiency of scale-up and other pharmaceutical workflows, making them simpler, safer, faster, and more sustainable.
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X-ray fluorescence (XRF) spectroscopy provides many benefits over traditional elemental analysis techniques for pharmaceutical applications, including inductively coupled plasma (ICP) spectrometry. ICP techniques1 require highly skilled operators as well as hazardous and time-consuming sample preparation. In contrast, XRF sample preparation is much faster, less complex, and doesn’t destroy the sampled material in the process. These improvements are particularly beneficial in the scale-up context, as specialized labor as well as drug substances and formulations are in short supply. XRF analysis therefore greatly improves the efficiency of scale-up and other pharmaceutical workflows, making them simpler, safer, faster, and more sustainable.
X-ray fluorescence (XRF) technology has been widely adopted as a quality control technique in many highly regulated industries, such as food, cement, and mining. Yet it has not been embraced by the pharmaceutical industry – even though it can provide many strategic and operational benefits in this context. While ICP spectroscopy provides a wealth of data on samples and plays a critical role in elemental analysis, its popularity can lead to bottlenecks and mounting costs as samples get held up in a queue and scientists wait for results. Incorporating XRF analysis into the pharmaceutical workflow – whether during early development, scale-up or manufacturing – can help relieve such bottlenecks. Furthermore, ICP instruments require highly specialized operators to perform the sample preparation, which involves dissolving the sample using hazardous chemicals and can take up to several days to complete. In contrast, sample preparation for XRF analysis is far less complex: no hazardous chemicals are used, operators do not require extensive training, and samples can be prepared and measured in under 30 minutes. In addition, pharmaceutical applications require orthogonal2 analysis to confirm results, so XRF analysis can be a very effective complement to ICP spectroscopy for elemental analysis.
Whereas ICP spectrometers strip ions from atoms in a sample and then measure those ions to identify the elements present, XRF instruments use high-energy radiation to excite the electrons around the atoms. At this point, the electrons emit fluorescent X-ray ‘fingerprints’ characteristic of their specific element. The key difference from ICP spectroscopy is that the electron excitation is non-destructive. Samples analyzed using XRF systems can be re-analyzed with the same or a different technique and even returned to production. This is a major benefit in any application where samples are precious, such as the development of active pharmaceutical ingredients (APIs). Indeed, the development of an API can be very expensive, and production capabilities in the early stages of drug development can be limited.
When comparing XRF spectroscopy and ICP spectroscopy for drug development, the key features are ease of operation, speed of the analytical feedback loop, and instrument accuracy and sensitivity.
Salutas Pharma GmbH published a paper4 on the choice of benchtop XRF instrument over other techniques (including ICP-OES5 and LA-ICP-MS).6 Their reasons for choosing XRF technology included:
Following a recent trial of Malvern Panalytical’s Revontium™ XRF instrument, a laboratory manager familiar with ICP analysis told us that XRF analysis provides better results than ICP analysis for drug products containing chlorine and bromine salts.
In another case, the chief technical officer of a contract research organization highlighted the speed and ease of sample preparation for XRF analysis, which reduces the likelihood of errors. They also noted that because larger amounts of sample can be analyzed with an XRF system, it provides better sample representation. They added that the non-destructive analysis of XRF also allows for subsequent analysis with other techniques, further improving confidence in results.
As XRF instruments do not require the use of solvents, reagents, gases, or daily calibration, the running costs are substantially lower compared to ICP instruments. Overall, Malvern Panalytical XRF instruments have up to 50% lower operational costs compared to traditional ICP instruments. What’s more, because XRF spectrometers do not require dedicated and highly specialized operators to deliver robust results, users will quickly realize a return on their investment thanks to the simplicity of XRF technology. One customer in the pharmaceutical industry told us that nine within nine months of introducing an XRF system into their workflow, they were able to save the costs of one full-time ICP operator.
Another cost benefit of XRF analysis over ICP spectroscopy, according to one laboratory manager we spoke to, is that method transfer is easier and cost-free with XRF, whereas method transfer from one ICP instrument to another costs around $25,000. |
Operationally, XRF technology greatly speeds up analytical feedback loops by allowing samples to be measured directly or with minimal preparation, which also eases method transfer. Results are thus obtained faster, removing elemental analysis as a bottleneck to other processes in drug development and manufacturing workflows.
Finally, the small footprint of some XRF instruments and the fact that they don’t require additional infrastructure (such as fume hoods and extraction equipment) mean it’s possible to place XRF instruments at-line for optimal efficiency.
The EFPIA7 has laid out several targets for more sustainable practices in the pharmaceutical industry, in line with the desires of stakeholders and industry leaders. Moving to more sustainable analytical techniques can help drug developers achieve these targets by reducing the use of non-renewable materials and synthetic chemicals. In one example, such green chemistry efforts resulted in a 19% reduction in waste and 56% improved productivity compared with past drug production standards.8 XRF technology can contribute to a sustainable chemistry strategy because it eliminates the need to use hazardous reagents
Removing the use of hazardous chemicals also greatly improves safety for operators. Effective management of chemical risks linked to the handling of these agents is mandatory for the safety of the workers in the industry, as per the rules and guidelines of various acts regulating the pharma industry.
Incorporating XRF analysis into your workflow can form part of a green chemistry strategy, helping to increase sustainability in terms of environmental impact and health and safety for operators.
Malvern Panalytical’s XRF solutions are designed to provide precise and fast elemental analysis with a focus on ease of use, low implementation costs, and low operational costs.
Epsilon 1 | Epsilon 4 | Revontium | |
---|---|---|---|
Overview | Get started | Automate for higher throughput | Automate; prepare your methods for QC and full regulatory compliance |
Sensitivity | ✓ | ✓✓ | ✓✓✓ |
Measurement time per sample | 10 minutes to analyze 5 elements | 45 minutes to analyze 20 elements according to ICH-Q3D | 30 minutes to analyze 20 elements according to ICH-Q3D |
Sample throughput (automation) | 1 | 10 | 32 |
Catalyst residue according to ICH Q3D guideline | ✓ | ✓ | ✓ |
Detection of toxic elements, e.g. ‘Big 4’: Cd, Pb, As, Hg [big 4 or toxic 7] according to ICH Q3D guideline | -- | ✓
1 g daily dose* | ✓✓
10 g daily dose |
Detect wear elements (Cr, Mn, V, Ni, Cu) | ✓ | ✓ | ✓ |
* Suitable for pharmaceuticals where the total mass of drug product consumed by a patient daily does not exceed the given value.9
Malvern Panalytical’s Revontium and Epsilon instruments comply with the US Pharmacopeia (USP <232>, USP <233>), where XRF spectroscopy is mentioned explicitly as a suitable technique for metal impurities testing (USP<735>). XRF spectroscopy is also described in the European Pharmacopoeia (2.2.37) and complies with the ICH Guideline for Elemental Impurities (Q3D).
Malvern Panalytical’s software supports customers working in a regulated environment across its range of XRF instruments, simplifying measurement auditing. Regulatory compliance and data integrity can thus be achieved quickly and with full confidence.
An XRF instrument is an effective investment as an alternative, complementary, or orthogonal technique to traditional elemental analysis techniques, such as ICP spectroscopy for elemental analysis for pharmaceutical development and manufacturing. Compared to ICP instruments, XRF systems does not require extensive training, and the removal of hazardous materials for sample preparation greatly improves worker safety and sustainability. The much more direct analysis provided by XRF technology results in much faster sample preparation, easier and cheaper method transfer, and faster screening speeds. Overall, XRF analysis is well-adapted to pharmaceutical and API scale-up applications, complying with industry standards and providing key strategic and operational benefits.
If you are interested in how applying XRF analysis to your pharmaceutical applications, please contact Malvern Panalytical for more information or to arrange a demonstration.