Metrohm PTRam Process Development Raman Analyzer

Significance of the Topic

Raman spectroscopy has become an essential tool in process analytical technology (PAT) for pharmaceutical, biochemical and polymer industries. It enables real-time, non-destructive monitoring of chemical composition, crystallinity and reaction progress. The availability of robust, high-performance analyzers that can operate in both laboratory and pilot-plant environments supports accelerated development, improved quality control and regulatory compliance.

Objectives and Overview

This document presents the PTRam™ Process Development Raman Analyzer, a 19-inch rack-mountable spectrometer designed to meet the needs of product and process development laboratories. Key goals include delivering precise spectral data, ensuring instrument stability and providing automated validation features for continuous operation.

Used Instrumentation

• PTRam™ Raman Analyzer, model BWS476-785H
• 785 nm diode laser delivering up to 340 mW at sample
• Single-channel fiber-optic probe (lab-grade, 1.5 m, BAC100B-785-HT)
• Vision® spectroscopy control and data-analysis software (non-Pharma and optional Pharma 21 CFR Pt 11 versions)
• ASTM polystyrene validation standard (NR-PCC) for resolution calibration

Methodology and Instrumentation Details

The PTRam™ employs a 785 nm laser source with software-adjustable power (0–100% in 1% increments) and a spectral range spanning 150–2800 cm⁻¹. Spectral resolution is better than 6 cm⁻¹ (measured at 912 nm), compliant with ASTM E2529-06 guidelines. Internal reference standards enable automatic Raman shift calibration. The system interfaces via USB 3.0, operates over 15–30 °C, and supports continuous 24/7 monitoring.

Main Features and Performance

• High stability laser ensures consistent excitation over extended periods
• Rugged spectrometer design suitable for pilot-plant environments
• Automatic self-calibration and system validation routines enhance data reliability
• Fast warm-up time (5 minutes) minimizes downtime
• Power consumption under 100 W allows flexible laboratory deployment

Applications and Practical Benefits

The PTRam™ system addresses a broad range of process development challenges:

• Pharmaceutical API synthesis: reaction monitoring, yield assessment
• Crystallization and polymorph transitions: tracking solid-state changes
• Formulation processes: blending, granulation and drying validation
• Bioprocess analysis: fermentation progress and metabolite profiling
• Polymerization and extrusion: online polymer and blend characterization
• Catalysis investigations: monitoring catalyst activity in real time

Users benefit from streamlined workflows, reduced offline sampling, improved process understanding and enhanced regulatory compliance.

Future Trends and Potential Uses

Integration of Raman analyzers into automated PAT frameworks and advanced multivariate analysis platforms is expected to grow. Emerging trends include inline monitoring with high-pressure/temperature probes, machine-learning-driven spectral interpretation and seamless data exchange with digital manufacturing systems. These developments will further reduce development cycles and support real-time release testing.

Conclusion

The PTRam™ Process Development Raman Analyzer combines high performance, automated validation and flexible sampling accessories to meet the demands of modern process development and quality control. Its robust design and comprehensive software support make it a versatile tool for laboratories and pilot plants aiming to implement advanced Raman-based PAT strategies.

References

• ASTM E2529-06, Standard Guide for Testing the Resolution of a Raman Spectrometer
• B&W Tek, LLC, PTRam™ Process Development Raman Analyzer, 2021