Presentation MicroNIR by Emiliano Genorini Nov 14th Rijksmuseum

1© 2016 Viavi Solutions Inc.www.viavisolutions.com
Critical attributes
process monitoring by NIR
Amsterdam (NL), November 14th 2019
Emiliano Genorini
MicroNIR Americas and EMEA Account Manager
+39 039 9300225 (office) | +39 337 1362987 (mobile)
Via Cernuschi, 8 | 20900, Monza (MB) - Italy

2© 2016 Viavi Solutions Inc.www.viavisolutions.com 2© 2016 Viavi Solutions Inc.www.viavisolutions.com
Company profile

Company Profile - Viavi Solutions

Our vision

MicroNIR - Our vision

Liner Variable Filter

Product line - LVF
• Small size allow special applications
• No moving parts:
- no misalignments
- stability over long time
- 100% transferability between units
• No fiber optics:
- no possibility to break it
- no ageing
- insensible to temperature fluctuation
• Small distance → high energy and S/N
→ from traditional benchtop to sensor

Process Analytical
Technology

MicroNIR - PAT

High Shear Mixer

FluidBed
Dryer
HighShear
Granualtor
MicroNIR - Granulation and Drying
Multi steps
process
Mixing
Granulation
Discharging
Wet mass calibration
Drying
Cooling
Calibration
Discharging
HighShearGranualtor
Single step
Process I
Mixing
Granulation
Drying
Cooling
Calibration
Discharging
FluidBedGranulator
Single step
Process II
Mixing
GranulationDrying
Drying
Cooling
Calibration
Discharging

MicroNIR - Granulation and Drying
On line monitoring
• Impeller torque for granualtion
end point
• INOUT air temperature for
drying end point
• INOUT air humidity for drying
end point
Pros
• Real time online measurement
• No sampling required
Cons
• Physical measurement
• Indirect analysis of particle size
and moisture content
At line monitoring
• Particle Size Analyzer for
granualtion end point
• Karl Fischer or Loss on Drying
(LOD) for drying end point
Pros
• Direct analysis of Particle Size
andor moisture
• Chemical measurement
Cons
• Sampling required
• Lab measurement
• Long time compared to process
duration  (start) and final

MicroNIR - High Shear MixerInstallation
IMA device with MicroNIR PAT U
mounted on VIAVI welded flange

MicroNIR - High Shear MixerPreprocessed Spectra
Liquid bridgeSolid bridgeSnowball
Spectra 1der+SNV

MicroNIR - High Shear Mixer - MBSD
Dry Mixing
Wetting
(Primary
Granulation)
Massing
(Secondary
Granualtion)
■ Impeller Torque
■ MBSD
■ MBM

Fluid Bed Dryer

MicroNIR - Fluid Bed Granulation - Spectra
• Collected datas are correlatd to physical
variables like Moisture and Particle Size
Distribution
• It is necessary to collect physical datas
manually to build a calibration curve.
• The Partial Least Square method is used to
calculate the correlation grade, represented
by R2, the closer is to 1, the better the
correlation is

MicroNIR - Fluid Bed Granulation - LOD
0.00
2.00
4.00
6.00
8.00
10.00
12.00
-15 5 25 45 65 85 105 125 145 165
LOD(%)
Sample Number
LOD Predicted Vs Real
Predicted LOD Real LOD

MicroNIR - Fluid Bed Granulation - D50
0.00
50.00
100.00
150.00
200.00
250.00
300.00
350.00
400.00
450.00
500.00
0 20 40 60 80 100 120 140 160 180 200
D50(µm)
Sample Number
d50 Predicted Vs Real
Real D50 Predicted D50

Blending

MicroNIR - Blending - Theft Sampling
• Labor intensive
• Expensive
• Poor reproducibility
• Blender must be stopped
• Perturbation of blending
• Long time to have feed back
• Contributes to sample non-uniformity
• Cross contamination
• Using of solvents
• Potential for exposure of operators to high potency API

MicroNIR - Blending - Theft Sampling
• Sampling errors 10-50 times
greater than analytical errors!
• Non-reproducible, therefore
cannot be corrected for
statistically
• QbD requires isolation of the
greatest source of variability
(sample thief)
Sample thieves de-mix
powder beds resulting in
heterogeneity increase

• Blending homogeneity is not content uniformity API %
• Question is not how much API you have but if it has been blended → if you want
to know how much is the API you weigh the API before mixing (more accurate)
Make PLS working and validate it from 0 to 100% of API is very challenging:
- Calibration deployed at line are not valid at line
- How can you build this on line? If you make spiking of API at line you could
have a reasonable number but it is hard to validate
- If you withdraw a sample you damage you blending
• Building a PLS requires to validate the method and register (documentation cost
that is 100x the cost of HPLC)
• It is only for valid for production not for R&D

MicroNIR - Blending
• Rotation Time
• API concentration
• Excipients
• Particle Size
• Blender Capacity
• Rotation Rate
• Fill level
• Loading Method (symmetric vs. asymmetric)

MicroNIR - Blending

MicroNIR - Blending
0
0.02
0.04
0.06
0.08
0.1
0 25 50 75 100 125 150 175 200
Problem Blend
Model Blend

MicroNIR - Blending
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.1
0 5 10 15 20 25 30 35 40
Rotation Number
5 Liter Bin
10 Liter Bin
40 Liter Bin
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.1
0 5 10 15 20 25 30 35 40
Rotation Number
15 rpm
25 rpm
32 rpm
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.1
0 10 20 30 40 50 60 70 80
60% Filll
75% Filll
90% Filll
0
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.1
0 5 10 15 20 25 30 35 40
Rotation Number
Active Layered - Centered
Active Spot - Off Center

Tableting

MicroNIR - Feed frame

Talc

Talc 1% Talc 3% Talc 5%

Presentation MicroNIR by Emiliano Genorini Nov 14th Rijksmuseum

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