Metrohm PTRam Process Development Raman Analyzer

Importance of the topic

Raman spectroscopy offers a non‐destructive, reagent‐free approach to obtaining molecular fingerprints in real time, making it indispensable for process development, quality assurance, and analytical research in pharmaceutical, polymer, and bioprocess industries. Its ability to monitor chemical changes without extensive sample preparation accelerates optimization of reactions, crystallization, and manufacturing workflows.

Study objectives and overview

This summary covers the PTRam™ Process Development Raman Analyzer, a 19″ rack‐mountable system designed by B&W Tek for use in analytical laboratories and pilot plants. The instrument is engineered to provide stable, high‐resolution Raman spectra and automated validation, supporting diverse process analytical technology (PAT) applications.

Methodology and instrumentation

The PTRam™ system integrates the following key components and features:

• Laser source: 785 nm diode laser delivering up to 340 mW at the sample, with software‐controlled power adjustment in 1 % increments.
• Spectrometer: High‐performance optics achieving <6 cm⁻¹ resolution over a spectral window of 150–2800 cm⁻¹ (measured per ASTM E2529-06).
• Sampling probe: Single‐channel, 1.5 m fiber‐optic probe (BAC100B-785-HT) with user‐replaceable shafts for immersion, high‐pressure/temperature, and extrusion applications.
• Self‐calibration and validation: Internal reference standard enables automated wavelength calibration and performance checks in compliance with USP/EP guidelines.
• Software interface: Vision® software (Windows-based) for data acquisition, method development, system monitoring, and compliance testing; optional 21 CFR Part 11–compliant Vision Pharma version available.

Main results and discussion

As a specification‐driven analysis, the PTRam™ demonstrates:

• Rapid readiness: Warm-up time of approximately 5 minutes, enabling fast deployment.
• Continuous operation: Reliable laser stability and automated monitoring support 24/7 data collection.
• High data integrity: Self‐monitoring ensures consistent spectral quality for routine PAT implementations.
• Modular adaptability: A range of optional probes and accessories allows tailored configurations for crystallization monitoring, API yield studies, polymer blending, fermentation tracking, and catalysis research.

Benefits and practical applications

• Process insight: Real‐time feedback on reaction progress and polymorph transitions improves efficiency in API development.
• Versatility: Applicable to pharmaceutical formulations (blending, granulation, drying), bioprocessing, polymer science, and biomedical research.
• Regulatory alignment: Automated system checks and validation tools facilitate PAT/QbD compliance and pharmacopeial standards.
• Scalability: Rack‐mount form factor and extensive accessory options support smooth scale‐up from laboratory investigations to pilot‐scale production.

Future trends and applications

Advancements are expected in integration with multivariate analysis and machine learning algorithms for predictive process control, coupling Raman with complementary spectroscopic techniques for comprehensive monitoring, and development of portable, wireless variants for remote, in-line analysis. Continued improvements in detector sensitivity and laser technology will expand detection limits and measurement speed.

Conclusion

The PTRam™ Process Development Raman Analyzer provides a robust, high‐resolution platform for real‐time chemical analysis and process monitoring. Its self‐calibration, modular probe options, and comprehensive software suite make it a versatile tool for accelerating R&D, ensuring consistent product quality, and meeting regulatory requirements.

Instrumentation used

• BWS476-785H Raman spectrometer with 785 nm, 340 mW laser.
• Fiber‐optic sampling probe BAC100B-785-HT (1.5 m).
• Vision® spectroscopy software and optional Vision Pharma (21 CFR Part 11).
• Optional accessories: immersion shafts (RIS100 series), high‐pressure/temperature shafts (RIS100-SS/HS), hot‐melt extrusion shafts (RHS100 series), flow cells (BAC160), probe holders & XYZ stages (BAC151B), and large‐area probes (BAC102-785-ST).