Transcript
TruProcess Near Infrared Analyzer
Kurt Kortokrax
Thermo Scientific
Account Manager
Kurt.Kortokrax@thermofisher.com
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Thermo Scientific TruProcess NIR Process Analyzer
Spectral Range 1600-2400 nm (6250-4100 cm-1)
Absolute Wavelength Accuracy +/- 0.1 nm
Wavelength Calibration Internal software controlled wavelength standard for on-the-fly calibration and
qualification.
Measurement time <0.75 sec. per spectrum
Sampling Mode Non-Contact diffuse reflectance
Working Distance Nominal working distance - 35 – 50 mm
Maximum recommended working distance - 100 mm
Sampling area 25 mm @ 50 mm working distance
Size 177 mm (l) x 127 mm (w) x 158 mm (h) standard configuration
Weight 2.95 kgs (6.5 lbs)
Enclosure & materials
Aluminum, dust and waterproof, o-ring sealed enclosure with durable and
cleanable powder coated surface, stainless steel tri-clover fitting, and sapphire
isolation window.
A/D Converter 24 bit
Position Trigger Integrated MEMS accelerometer for dynamic blending applications
Detector Single InGaAs w/2 stage cooling
Source Dual 5 watt tungsten NIR source
Software included: SpectralCode Plus™, SpectralCode Direct Command Set
Operating Systems Windows XP, Vista or Windows 7
Computer Interface Ethernet, RS232 serial, USB, and wireless with router
Operating Temp Range 0 to 35°C (non-condensing).
Storage Temp Range
-40 to +85°C
Power Batteries: 2 x 5AH 7.2 Lithium Ion (4.5 hour run-time)
External Power: 7 – 14 Volt DC (2.5 amps max)
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TruProcess Near Infrared (NIR) Process Analyzer
• Non-Destructive: Non-contact diffuse reflectance measurement with programmable acquisition trigger
• Fast, accurate monitoring: Wireless communications with real-time data analysis and storage
• Customizable: TruProcess is compatible with Thermo Scientific Method Development software which
allows for both qualitative and quantitative applications including; drying, blending and moisture analysis
• Advanced Technology: Micro-electrical Mechanical (MEMS) technology transforms traditional NIR
technology into a process-line NIR sensor
Advantages of MEMS technology
• Smaller size and portability: Allows for quick deployment across
large process manufacturing environments
• Reliability: MEMS technology has no moving parts with proven
reliability
• Reproducibility for method transfer: Internal wavelength calibration
provides superior wavelength accuracy
• Speed: The MEMS engine has a scanning speed up to five
microseconds and blending rates up to 25 rpm
• Scalable from bench scale to full manufacturing scale
• Reduced deployment costs and long term cost of ownership
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TruProcess Analyzer Configuration
Wireless “Wi-Fi”
antenna to transfer
Real-time spectra to
external PC/station
2 Light sources
with 2.5” tri-clover
connection for
easy installation on
blenders & dryers
Integrated Standard
materials for performing
background and PQ
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Technology- MEMS (Micro ElectroMechanical Systems)
Unactuated: incident
light reflected
Actuated: programmable
filtering at 1/4- wavelength
displacement
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TruProcess Analyzer Configuration
DC power, RS232,
USB, Ethernet
connections
Hot-swappable
batteries ports,
rechargeable Li-Ion
batteries for up to 5-6
hours of continuous
operation
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Near Infrared is ~ 800-2500 nm region 1nm = 10-9 meters
Electromagnetic Spectrum
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Near Infrared Spectroscopy
• The observation of how electromagnetic energy (Near Infrared) interacts
with a sample
• NIR light is all around us – It is the part of sunlight that carries the heat
• A simple quartz tungsten-halogen bulb is used as a source of NIR
• Many substances will interact with infrared light by absorbing at specific
frequencies that are unique to that material
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Example: C-H Overtones
First Overtone
3378 nm (C-H Stretch) * 1/2 = 1689 nm
Second Overtone
3378 nm (C-H Stretch)* 1/3 = 1126 nm
Overtones
SpectralCode Plus Software
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SpecralCode Plus Software
• “Real-time” acquisition of spectral data
• Standard pre-process functions (SNV, MSC, 1st ,2nd Deriv.
Normalization, etc.)
• Qualitative algorithms
• Standard Deviation (MBSD)
• PCA
• Quantitative algorithms:
• PLS1
• “Real-time” trending of multiple Qualitative and/or Quantitative
results
• Saving all results, spectra, etc.
• Adjust triggering time delay based on blender fill
• Off-line models testing capability
• Process interfaces to PLCs using Ethernet connection
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SpecralCode Plus Software
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Triggering
• Power Monitor Method
• Optical power monitoring is good enough to detect onset of cascading
material
• Gravity Method
• Fully software programmable MEMS Accelerometer
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Real-Time Prediction and Trending
TruProcess Applications and Usage
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Process Analytical Technology and NIR
• Real time monitoring and control of process parameters and
material performance attributes
• NIR devices well suited for at-line, in-line and on-line measurements
• Rapid determination of physical and chemical properties of
raw materials, intermediates and final dosage forms
• Chemometric analysis from data acquisition to statistical process control
• Multivariate analysis for quantitative assessment
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At point-of-use application in Pharmaceutical Manufacturing
Receiving warehouse:
100% verification of receivables.
Detection of common contaminants.
Quantification of ingredient moisture content.
Dispensing: 100% Final verification of ingredients.
In process: Reaction completion Determination of moisture content
Solvent exchange monitoring
Finished Product: Determination of ingredient ratios.
Content uniformity.
Thickness of tablet film coatings.
Packaging: Verification of packaging polymers.
Determination of polymer thickness.
Clinical trial: Spot verification of placebo and active doses.
Post-production: Degradation analysis of retained samples. Counterfeit products evaluation
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Monitoring Blending and Drying Processes
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TruProcess Scalability
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Real-time Blend Uniformity by using TruProcess Analyzer
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Sco
re:
1=
pu
re c
om
po
nen
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Measurement #
Lac
MgS
Stdev - Lac
Stdev - MgS
1 kg APAP Added 60 g MgS Added
1 kg Lac Added • Standard deviations
calculation
• Lac/APAP Scores are
calculated using the
difference between
pure Lac and APAP
• MgS scores are
calculated using the
difference between
MgS and the Lac/APAP
blend.
Real-time Blend Uniformity by using TruProcess Analyzer
Blending
Good
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Full-spectrum PCA trending
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• PCA - 1 factor
• Savitzky-Golay 1st Derivative
• Use range 1976-2067 nm Score F1
Suspected
Acetaminophen
issue
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Trending
• Spectral difference model
• Savitzky-Golay 1st Derivative
• Normalize Range
• Trending is similar to other
methods, but some quantitative
information is present.
• Recommendation:
• Follow standard deviation until it
falls below target value
• Follow quantitative value until if
falls below target value
0.55
0.65
0.75
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0.95
1.05
0 50 100 150 200 250 300 350
0
0.005
0.01
0.015
0.02
0.025
0.03
0.035
0.04
0.045
0.05
5-point symmetric stdev
15-point historic stdev
“PLS” prediction
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Real-time API Blending by using 2 TruProcess Analyzers
• 3.5 Quart Stainless steel V-Blender
• 8 compounds formulation
• Spectra were collected with Gravity sensor
- 1 scan every rotation
- 22 rotation per minute
• Modeling done using PLS
• RMSNV (Root Mean Square to the Nominal Value) was uses to monitor blend homogeneity
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Results
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Rotations
Concentr
ations
APAP
MCC
MGST
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0.2
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1.2
Rotations
Concentr
ations
APAP
MCC
MGST
Sensor 1 Sensor 2
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• Analyzer communicates with external PC via
standard wireless (Wi-Fi) Ethernet connection
• TruProcess NIR Analyzer was installed on viewing
window of Glatt FBD without any dryer
modification.
• Standard tri-clover connection was used, allowing
to relocate analyzer easily without any tools.
Real-time on-line Moisture content by TruProcess
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Real-time on-line Moisture Content by TruProcess™
• Every 15 sec.
• RMSEC - 0.17%
• RMSECV - 0.17%:
- Reference validation results
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Real-time moisture prediction
Prediction was performed for first 3 hours of 9 hours of granulation/drying process using
previously created Quantitative PLS1 calibration/model
Reference validation results
3:20pm 3:50pm 4:20pm 4:50pm 5:10pm
Time (July 27, 2010)
Qualification and Connection to External
Systems
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Regulatory Solution
Traceable Standards
USP 1119 Qualification Protocol
IQ Installation
Qualification
PQ Performance
Qualification
OQ Operational
Qualification
Methods
RESULTS
Data
Qualification
Procedures
Traceable
Standards
USP 1119
Protocol
Method
Development
LCD Display
Archive
LIMS
PLCs or DCS
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Performance Qualification and
background spectra collection
can be performed
AUTOMATICALLY
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Regulatory Solution
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