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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0

0.05

0.1

0.15

0.2

0.25

0.3

-0.5

-0.3

-0.1

0.1

0.3

0.5

0.7

0.9

1.1

0 100 200 300 400 500 600 700

Sco

re:

1=

pu

re c

om

po

nen

t

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

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0 50 100 150 200 250 300 350

• 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

0.85

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

0 50 100 150 200 250 300-0.2

0

0.2

0.4

0.6

0.8

1

1.2

Rotations

Concentr

ations

APAP

MCC

MGST

0 50 100 150 200 250 300-0.2

0

0.2

0.4

0.6

0.8

1

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

Shutter closed Shutter open

Regulatory Solution