Process Analytical Technology

Lighthouse Probe® - online measurement

The Lighthouse Probe® can be used for real-time monitoring of chemical and pharmaceutical processes and provides in-process window cleaning at any time, recalibration during the process, full CIP of wash housing and seal, and a clear view inside – even in difficult conditions.

Compact & Cleanable In-process Optical Probe

The Lighthouse Probe® enables PAT

The biggest flaw of optical spectroscopy is the dependency on a clean observation window. When window fouling occurs during process, it will eventually lead to wrong analysis results, unwanted process stops and bad product quality. Since on-line and in-line optical analysis becomes more and more important, reliable and robust systems capable of overcoming this flaw, are needed. 

Though various vendors made attempts to overcome the issue using window heating and blow off systems, none of these ‘solutions’ seemed to work over longer time span. And all of them had the same flaw: once the fouling occurred, there was no way of recovering. To ensure an optical detection that can overcome these issues and check its status during the process, the Lighthouse Probe® was developed. The probe has window cleaning capabilities and an internal reference to overcome a second frequently encountered issue namely reference contamination. Both these functions can be used in process without breaking containment. 

The Lighthouse Probe® comes in 2 different types:

  • Manual probe
  • Automated CIP probe

The probes can be upgraded from manual to automated CIP alongside with the development of your product from laboratory to production. They can be delivered matching a variety of spectrometers.

Benefits

  • Time savings: The Lighthouse Probe® can be used for realtime release. 
  • Resources savings
  • Materials savings

Example:

During the FAT of a Consigma® tableting line, the Lighthouse Probe® was used for on-line moisture analysis: The moisture of the final granulate was available in real time while off-line lab analysis took one week to analyze only one third of the samples (time savings).

The difference in resources savings consumption during that same FAT was 2 man-week of lab analysis (and lab-consumables).

Because of the direct availability of the analyzer data, deviation from the desired quality is detected immediately and corrections were made based on that data and the process moved back to optimal quality before even going out of spec. The offline analysis of one sample took 12 minutes (optimal case) so the minimal waste in case of a bad result in case of off-line analysis is 5 kg (throughput of the machine being 25kg/hr) (material savings)

Summary

The Lighthouse Probe® provides:

  • In-process window cleaning at any time.
  • Recalibration at any time during the process
  • Full CIP of wash housing and seal
  • Always a clear view inside, even in difficult conditions

Use Case: Granulation endpoint detection

High Shear Granulation Endpoint Detection

Online Process Monitoring

  • Suitable for monitoring blend homogeneity, moisture, density (by correlating spectra) and physical granule properties (by correlating scattering effect)
  • More consistent batches resulting in better tablets
  • Non-destructive and direct online analysis of granule quality
  • Very fast spectroscopic technology using Diode Array Detector (other spectroscopic technologies possible)
  • Reliable and robust process interfacing to guarantee representative measurements.
Main Benefits
  • NIR spectra contain physical and chemical information about the measured product, allowing good correlations with traditional granulation parameters like density, particle size etc.
  • Using the Lighthouse Probe® – DAD sensor for endpoint determination will give more consistency between batches in granule properties, enabling optimisation of subsequent processing steps.
  • Less waste thanks to a more consistent quality of the batches. Real-time availability of the product data like moisture content and density will decrease risks and reduce waiting time for the finished batch to be released to the next processing step.
  • Because of the fast moving product during granulation, short measurement cycles are needed. The latest Diode Array Detectors can take spectra in only a few milliseconds, allowing the customer to take chemical images of very small quantities of material or, by averaging these spectra over time, to adjust the measured volume of product to what is normally used in offline measurements. Other configurations are possible but speed of measurement is traded-off against the gain in resolution.
  • More accurate modelling thanks to the possibility to clean the probe prior to taking a reference measurement for modelling.
  • Enhanced reliability thanks to the automation of the system. The LightHouse Probe® – DAD will perform a health check prior to usage to guarantee a correct measurement during process. This health check can also run online during production to ensure correct endpoint determination.
Suggested Configuration

For initial test work or for mobile test equipment, a manual probe is suggested while automated wash and CIP probes are designed for production. 

For single pot processing including drying, a CIP probe is advised combined with a complete integration to change models between granulation and drying regime.

The LightHouse Probe® fits on a standard 2” port, standard adaptor or weld-in ports can be provided. It is available as manual probe, automated wash probe and automated CIP probe.

Case Study

Genzyme reduces probe fouling and improves NIR data using the Lighthouse Probe®.

In 2011, Genzyme, at the time one of the world’s leading biotechnology companies, was looking for a PAT solution to control the high shear granulation of a development product by measuring a critical product attribute, rather than relying purely on time based processing or impeller current loading. The company used an optimized Lighthouse Probe® to get representative NIR data of a granulation process. Read the article to learn how the data was then correlated to moisture content, bulk/tapped density and particle size of the final product.

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