Rapid Screening for Elemental Impurities During Drug Substance Development

In this masterclass, Nancy Lewin and Paul Kippax dive deep into the advantages of using X-Ray Fluorescence (XRF) technology for rapid elemental impurity screening during drug development. This process has proven to be cost-effective, faster, and less resource-intensive compared to traditional ICP-based methods. If you're in the pharmaceutical industry, and you’re working on metal catalyst scavenger screening or the analysis of elemental impurities you won’t want to miss this one. 

The Challenge: expensive and time-consuming screening methods 

Nancy shares the initial problem that led her to XRF: "We were doing some ICP optical work for screening samples, and the solvents used were hard on the instruments. It was cost-prohibitive and a massive time drain." She explains how the team had to replace torches, tubes, and other equipment frequently, which slowed down processes and frustrated lab technicians. It became essential to find a new method that could reduce costs and speed up analysis. 

Why XRF? 

Nancy found that XRF offered several benefits: 

• Cost Reduction: "XRF wasn’t just about saving money on equipment—it also reduced the cost of consumables and reagents." 
• Faster Analysis: Traditional ICP methods required extensive calibration and sample preparation, while XRF allowed the team to get results in a fraction of the time. 
• Resource Optimization: Fewer reagents and less preparation meant the process was easier on both human resources and lab facilities. 

Paul added that, in today’s pharmaceutical landscape, "there’s a strong need to improve pipeline efficiency, and XRF is perfect for fast response times." 

From Walk-Up Instruments to Easy Screening 

Process chemists were accustomed to using walk-up instruments for methods like HPLC, but ICP-MS systems posed challenges. XRF, however, provided an easy solution that allowed chemists to perform screenings independently, without needing an in-depth analytical chemistry background. This democratization of technology was a game changer. 

Nancy reflects on this transformation: "The chemists were thrilled to have a screening tool that didn’t require extensive technical knowledge. XRF gave them control over their work and provided fast, reliable results." 

Case Studies: XRF in Action 

• Study 1: Palladium Scavenging in Process Chemistry
  One of the major applications of XRF was in the screening for residual catalysts like palladium, which are critical in drug synthesis. Nancy shares a case study where XRF was used to optimize the removal of palladium, ensuring the drug met regulatory limits. 
  
  
• Study 3: Copper Scavenging
  Another example highlighted copper removal, where XRF screening helped optimize the synthesis process by allowing chemists to quickly assess the effectiveness of scavengers. 

Both studies demonstrated how XRF could complement traditional ICP methods by providing quick and actionable results at the early stages of synthesis. 

Advantages of XRF Screening 

Paul emphasized the significant benefits XRF offers, including: 

• Speed: With results in as little as 30 seconds to 2 minutes, it’s a much faster alternative to ICP methods. 
• Cost Efficiency: "When comparing the cost of an XRF system to an ICP-MS with all the bells and whistles, there’s a significant cost saving." 
• Ease of Use: XRF doesn’t require specialized facilities or exhaust systems, making it easy to integrate into labs. 
• Flexibility: XRF can be used for both liquid and solid samples, making it versatile across different processes. 

Conclusion 

XRF is an underutilized but powerful tool in the pharmaceutical industry. As Nancy states, "We’re just scratching the surface of what’s possible with XRF." By offering a faster, more cost-effective screening tool, it allows for greater flexibility and resource optimization in drug development. 

For more insights into XRF and its applications in pharmaceutical screening, listen to the full episode above or explore additional resources at Malvern Panalytical.