Microanalysis and Imaging

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Partnering for New Technologies for
Pharmaceutical Analysis
Process Analytical Technologies
Dan Klevisha Vice President

• Microanalysis and Imaging
• Tom Tague, Ph.D.
• Product Manager

Billerica, MA
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PAT initiative from a vendors viewpoint

• PAT initiative allows pharmaceutical companies to
  benefit from new and evolutionary process
  technologies as has already taken place in other
  industries
• Trends indicate increased utilization of new
  process technologies
  
• Increased production capacity and efficiency
• Lower production and monitoring cost
• Reduction/elimination of OOS

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Strategic Development Planning

• Partnerships for the development and evolution of
  PATs
  
• New applications of existing technologies
• On-line NIR blenders and dryers
• NIR and FT/Raman content uniformity
• Development of new technologies
• Spectral Imaging
• FTIR/cleaning validation

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FTIR/NIR/Raman Process Technologies

• Non-destructive
• Near real-time
• Highly applicable

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Applications in the Pharmaceutical Industry
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Polymorphic analysis
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Expanding the role of vibrational spectroscopy
in Process
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Online NIR blending and drying with fiber probes
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Process FT-NIR for Non-Contact Analysis

• Homogeneity
• Moisture content in Fluid Bed Dryer
• Blending and Homogeneity

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Content uniformity of Tablets
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RamsysTM Process FT-Raman System

• On-line FT-Raman capabilities
• 1064 nm excitation for reduced fluorescence
• Configuration also available for raw material ID

immersion probe 18 bar 80C probe body/ 180
probe tip NEMA 4 rated
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Technology Summary

• No one technique does everything
• Advantages of applying accepted technologies to
  PAT
  
• Laboratory proven techniques applied to
  manufacturing process control
  
• Application of research techniques
• Revolutionary technologies

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Development and application of new technologies

• Partnering prevents implementing technologies
  that are already obsolete at implementation
  
• Codevelopment of new technologies
• Development with GMP, GCP, GLP
• Provide comprehensive support for achieving
  validation and monitoring goals
  
• Software compliance
• Documentation

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SpotViewTM FTIR Cleaning Validation System

• Eliminate tedious swabbing with Direct Surface
  Sampling
  
• Fast accurate analysis with no weighing or
  quantitative dilutions
  
• Ideal for metal reactors, mixers and dryers
• Better than1 ug/cm2 sensitivity
• Measurements in less than 10 seconds possible

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Easier Microanalysis

• Rapid identification of
• materials, compounds, and
• contaminants
• Visual observation of sample
• Reflectance and ATR data collection
• ID of samples as small as 20 microns

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Research Microanalysis

• Identification of small particles
• Enhanced visualization of sample
• Transmission, reflection, ATR, grazing incidence
  infrared
  
• Full data processing capabilities

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Research Microanalysis

• Automation
• Sample stage
• Mapping of sample
• Focus
• Aperture
• ATR contact

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Map of large particle
Automatic scan of the overview image
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Identification by library search
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Chemical Imaging

• Focal plane array based
• MIR and NIR imaging
• 4096 spectra in 6 seconds
• Diffraction limited spatial resolution
• Chemometrics manipulation of images
• Correlation of known compound and functional
  groups
  
• Side-by-side comparison of visual and chemical
  images
  

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Visible image of bone tibia with corresponding
global infrared chemical image
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IR Spectra of Bone Tibia
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Chemical profile of CO3-2
Integrated intensity of 1415 cm-1 band
Integrated intensity of 1415 cm-1 band at x10
microns position
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FTIR Macro-Imaging IMAC TM
Imaging of larger areas (tablets)
Sample area 4 mm x 4 mm
Goal of 100 inspection! Value of partnership
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FT-Raman Microanalysis

• Quick and easy analysis
• Analysis through vials, bags, etc.
• Usually no fluorescence
• No water interference
• Mapping of sample
• 785 nm excitation available

RFS 100/S FT-Raman Spectrometer
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Mapping the surface of an aspirin tablet
Higher aspirin concentration
Aspirin tablet area for mapping
Lower aspirin concentration
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Mapping a substance within the tablet
Aspirin tablet area for mapping
Lower aspirin concentration
Higher aspirin concentration
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Mapping chemicals and properties within a tablet
Aspirin tablet area for mapping
Aspirin - ring
Reflectivity
Binder
Aspirin - OAc
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Cell analysis by FT-IR
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The future of PAT is indeed bright!

Thank you for your Attention