Process Analytical Technology

Gain efficiencies through gas analysis

The FDA’s Process Analytical Technology (PAT) initiative promotes improved process understanding by defining Critical Process Parameters (CPP) and monitoring these CPPs, either in-line or on-line. Processes can become more efficient, with reduced over-processing and greater product consistency.

Gain productivity by instituting a PAT program that is simple, data rich, and low-risk.

Featured PAT categories and resources

Product Drying
Use magnetic sector mass spectrometry to control the drying process with fast, precise, quantitative data

A key stage in many pharmaceutical processes is the complete or partial removal of a solvent or solvents from a product or intermediate. This drying process can occur in a variety of process vessels, including vacuum dryers, tray dryers and rotary dryers.

In the past, the success of the solvent drying process was simply measured at the end by taking a sample for laboratory analysis and the amount of residual solvent was defined by the Loss on Drying (LOD). If the sample failed the LOD test for one or more of the solvents then the drying process had to be restarted. If the drying took place under vacuum this provided additional complications in terms of both sampling the active pharmaceutical ingredient (API) and re-starting the dryer.

Mass spectrometers have been used to monitor solvent levels in the headspace above the API during drying processes but they have typically only produced qualitative or semi-quantitative data. If the MS is to be used as part of a PAT solvent drying process control project, it must produce accurate, reliable quantitative data, even for multi-dryer, multi-solvent systems. 

Featured product
Prima PRO VP Process Mass Spectrometer

Prima PRO VP can monitor up to 10 dryers, with a unique inlet that can switch between dryers at widely differing pressures and concentrations, and still provide reliable, stable solvent concentration data. Features include:

  • Magnetic sector MS, providing stable fragmentation patterns and resistance to contamination
  • 10-port Variable Pressure sampling inlet, able to handle process pressures between 1000 mBar and 0.3 mBar
  • Samples from headspace above the product, measuring the bulk API in the dryer and avoiding problems with grab samples caused by lack of homogeneity.
  • Easy, simple calibration with either gases or liquids ensures accurate quantitative data
  • 21 CFR Part 11 compliant GasWorks software 
Fermentation
Track fermentation processes in real time with fast, precise gas analysis

Analysis of respiratory gases is an ideal way of characterizing a fermentation process. It’s non-invasive and provides invaluable information on the physiological state of the culture, including growth kinetics and substrate consumption. It also helps determine the optimum point to halt the process for maximum yield. Many fermentations are characterized by small changes in oxygen and carbon dioxide concentrations. The speed of MS makes it ideal for the fermentation application but speed must not be at the expense of precision. It is equally important that precise data is acquired; otherwise, small changes in concentration will be lost.

Over 30 years of industrial experience have shown that magnetic sector analyzers offer the best performance for fermentation off-gas analysis. Key advantages include improved precision, accuracy, long intervals between calibration, and resistance to contamination. Typically, analytical precision is between 2 and 10 times better than a quadrupole mass spectrometer.

Featured products
Prima BT Bench Top Mass Spectrometer

Prima BT is a highly reliable, precise and flexible gas analyzer specifically designed for process development laboratories. Features include:

  • Scanning magnetic sector technology for fast, flexible, precise multi-component analysis. Concentrations of respiratory gases, inerts and volatiles can be measured in seconds with high levels of precision.
  • 16-port Rapid Multistream Sampler (RMS) for fast, reliable monitoring of multiple fermenters and bioreactors.
  • 21 CFR Part 11 compliant GasWorks software 
Prima PRO Process Mass Spectrometer

Prima PRO is currently the world’s leading process mass spectrometer, designed to operate reliably in harsh production environments and backed up with an industry-best three year warranty. Features include:

  • Scanning magnetic sector technology for fast, flexible, precise multi-component analysis. Concentrations of respiratory gases, inerts and volatiles can be measured in seconds with high levels of precision.
  • 32- or 64-port Rapid Multistream Sampler (RMS) for fast, reliable monitoring of multiple fermenters and bioreactors.
  • 21 CFR Part 11 compliant GasWorks software
  • Built-in air conditioner means Prima PRO can operate reliably over a wide ambient temperature range.
Product Drying
Use magnetic sector mass spectrometry to control the drying process with fast, precise, quantitative data

A key stage in many pharmaceutical processes is the complete or partial removal of a solvent or solvents from a product or intermediate. This drying process can occur in a variety of process vessels, including vacuum dryers, tray dryers and rotary dryers.

In the past, the success of the solvent drying process was simply measured at the end by taking a sample for laboratory analysis and the amount of residual solvent was defined by the Loss on Drying (LOD). If the sample failed the LOD test for one or more of the solvents then the drying process had to be restarted. If the drying took place under vacuum this provided additional complications in terms of both sampling the active pharmaceutical ingredient (API) and re-starting the dryer.

Mass spectrometers have been used to monitor solvent levels in the headspace above the API during drying processes but they have typically only produced qualitative or semi-quantitative data. If the MS is to be used as part of a PAT solvent drying process control project, it must produce accurate, reliable quantitative data, even for multi-dryer, multi-solvent systems. 

Featured product
Prima PRO VP Process Mass Spectrometer

Prima PRO VP can monitor up to 10 dryers, with a unique inlet that can switch between dryers at widely differing pressures and concentrations, and still provide reliable, stable solvent concentration data. Features include:

  • Magnetic sector MS, providing stable fragmentation patterns and resistance to contamination
  • 10-port Variable Pressure sampling inlet, able to handle process pressures between 1000 mBar and 0.3 mBar
  • Samples from headspace above the product, measuring the bulk API in the dryer and avoiding problems with grab samples caused by lack of homogeneity.
  • Easy, simple calibration with either gases or liquids ensures accurate quantitative data
  • 21 CFR Part 11 compliant GasWorks software 
Fermentation
Track fermentation processes in real time with fast, precise gas analysis

Analysis of respiratory gases is an ideal way of characterizing a fermentation process. It’s non-invasive and provides invaluable information on the physiological state of the culture, including growth kinetics and substrate consumption. It also helps determine the optimum point to halt the process for maximum yield. Many fermentations are characterized by small changes in oxygen and carbon dioxide concentrations. The speed of MS makes it ideal for the fermentation application but speed must not be at the expense of precision. It is equally important that precise data is acquired; otherwise, small changes in concentration will be lost.

Over 30 years of industrial experience have shown that magnetic sector analyzers offer the best performance for fermentation off-gas analysis. Key advantages include improved precision, accuracy, long intervals between calibration, and resistance to contamination. Typically, analytical precision is between 2 and 10 times better than a quadrupole mass spectrometer.

Featured products
Prima BT Bench Top Mass Spectrometer

Prima BT is a highly reliable, precise and flexible gas analyzer specifically designed for process development laboratories. Features include:

  • Scanning magnetic sector technology for fast, flexible, precise multi-component analysis. Concentrations of respiratory gases, inerts and volatiles can be measured in seconds with high levels of precision.
  • 16-port Rapid Multistream Sampler (RMS) for fast, reliable monitoring of multiple fermenters and bioreactors.
  • 21 CFR Part 11 compliant GasWorks software 
Prima PRO Process Mass Spectrometer

Prima PRO is currently the world’s leading process mass spectrometer, designed to operate reliably in harsh production environments and backed up with an industry-best three year warranty. Features include:

  • Scanning magnetic sector technology for fast, flexible, precise multi-component analysis. Concentrations of respiratory gases, inerts and volatiles can be measured in seconds with high levels of precision.
  • 32- or 64-port Rapid Multistream Sampler (RMS) for fast, reliable monitoring of multiple fermenters and bioreactors.
  • 21 CFR Part 11 compliant GasWorks software
  • Built-in air conditioner means Prima PRO can operate reliably over a wide ambient temperature range.