pat-enabling hard- and software
DESCRIPTION
PAT-enabling Hard- and Software. Andrey Bogomolov J&M GmbH, Germany. Outline. Good news in 2007 one more person started to earn his leaving from doing chemometrics J&M: the company Process monitoring J&M special equipment for PAT two industrial cases PAT philosophy - PowerPoint PPT PresentationTRANSCRIPT
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Andrey Bogomolov
J&M GmbH, Germany
PAT-enabling Hard- and Software
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OutlineOutline
• Good news• in 2007 one more person started to earn his leaving from doing
chemometrics
• J&M: the company
• Process monitoring• J&M special equipment for PAT• two industrial cases
• PAT philosophy• PAT chemometrics software concept • components making up a PAT solution
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J&M: IntroductionJ&M: Introduction
• About J&M GmbH• since 1987• spectroscopic equipment and components
specifically, UV-Vis/NIR, DAD, fiber optics, microspectroscopy
• positioned as “fast and precise”• recent years trend: spectroscopic equipment for PAT
• What kind of company?• strongly PAT-oriented• pro-chemometrics • active, growing• innovative • open-minded and collaboration-friendly
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J&M ProductsJ&M Products
Integrated in-situ Dissolution Test System
8-channel parallel Chromatography SystemTIDAS II NIR (1100 – 2100 nm)
NOVA fully-integrated Process Analyser
TIDAS fully-integrated spectrometer for pharmaceutical applications
Labo
rato
ryIn
dust
ry
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PAT and beyond…PAT and beyond…
• Process Analytical Technology (PAT)• is an initiative of FDA to create a regulatory framework for innovative
pharmaceutical development and quality assurance
• innovative methods [of data analysis=chemometrics] are allowed not only for research, but to provide the legal evidence (e.g. of product quality) for FDA
• the impact goes beyond the regulated environment, since any production is more or less bound with quality requirements
• The basic idea behind PAT is on-line process monitoring• product quality assurance
• process control
• process understanding
• process optimisation
• PAT and Chemometrics• chemometrics and spectroscopy are important components of PAT
• multivarite statistical process control (MSPC) replaces classical [univariate] statistics in the industry
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PAT players and driving forcesPAT players and driving forces
quality& safety
quality& safety
consumer
producer profit,
image
regulative organisatio
n
price
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LightHouse ProbeLightHouse ProbeTMTM (LHP) (LHP)
• Joint patent with GEA Pharma Systems
• Features and applications:• for on-line measurement of diffuse
reflectance NIR-spectra • e.g. granulation, drying, blending,
coating processes • through 7 sapphire windows• self-cleaning technology • multiple applications
moisture content, composition, homogeneity
particle size monitiring process end-point detection etc.
• Advantages (compared to surface-mounted probes):• reduced window fouling (cleaning) • enhanced contributing sample weight• better sampling: 3D-effect • => better performance
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Case 1. Moisture monitoring Case 1. Moisture monitoring
• Granulation and drying• granulation is routinely carried
out in the pharmaceutical production
• fluid-bed granulator• drying is the last step• proceeds to a sertain residual
moisture content (e.g. 2%)
• Moisture monitoring• process end-point detection• Loss on Drying (LOD) the direct
off-(at-) line technique
• PAT Classics• NIR monitoring of H2O is well-
established in-line technique 1200 1400 1600 1800 2000-0.1
0
0.1
0.2
0.3
0.4
Wavelength (nm)
Abs
orba
nce
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Case 1. Moisture monitoring (2)Case 1. Moisture monitoring (2)
r = 0.993RMSECV = 0.58a = 2
0 10 20 30 40 50 60 70 80 900
5
10
15
20
25
time (min)%
H2O
40 50 60 70 800
2
4
6
8
r = 0.996RMSECV = 0.17
a = 1 (!)
heating was interrupted
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Case 2. Pellet CoatingCase 2. Pellet Coating
• Polymer coating of pellets for capsule filling
• PrecesionCoaterTM • patented in 1998• well-controlled particle flow due to the Swirl
Accelerator
• Process conditions • constant heating; product temperature is
controlled• coating is followed by drying stage
• Materials• pellet size up to 1100 µm• layer thickness up to 30-40 µm
• Critical parameters• layer thickness • moisture content
• Is it possible to predict the dissolution profile?!
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Case 2. Pellet Coating (2)Case 2. Pellet Coating (2)
1200 1400 1600 1800 2000-2
-1
0
1
2
3
Wavelength (nm)
Abs
orba
nce
SNV-corrected spectra
0 50 100 150 200 250 3001100
1120
1140
1160
1180
1200
1220
time (min)
Par
ticle
dia
met
er (
m
)
0 50 100 150 200 250 3000
0.5
1
1.5
2
2.5
3
3.5
%H
2O
RMSEP = 0.12
a = 2
RMSECV = 4.05a = 3
moisture
predicted
deviation
calibration sample
particle size
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ProDicht ProjectProDicht Project
Probe window
Wash tubes
Movable Tip
Additional wash tube
Mirror
• On-going J&M project funded till 2010• Reutlingen University (Prof. R. Kessler)• University of Applied Sciences,
Offenburg (Prof. B. Spangenberg)• Light-Technical Institute, Karlsruhe• Laser technique by Optimags
• Spectroscopic probe for liquids• transmission and reflection modes• tunable pathlength• supports UV-Vis, NIR, IR, Raman,
Imaging, …• ability to combine multiple techniques
• Analysis in condense/ dispersive media• milk, creams, grease• fat content
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Technically, PAT is…Technically, PAT is…
• PAT = Hardware + Softwarere
• PAT hardware• sensors• analytical [spectroscopic] instrumentation• computers
• PAT software• instrument control software (data acquisition)• data processing and modelling (chemometric packages)• operating software (process visualisation, alarms, end-point
detection)• information/knowledge management software (LIMS)• PAT software !?
connect all hardware and aquire the data synchronise the data acquisition build and connect models predict, observe and operate process document the process
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Data handling software Data handling software
• Levels of data handling• data acquisition
instrument control, visualisation FFT, averaging
• data [pre-]processing baseline correction, smoothing,
derivation, subtraction, normalisation, peak picking, integration, transforms etc.
• [advanced] data analysis modelling decision making (chemometrics)
• information management LIMS, ERP, …
. .. …..
… .
acquire
process
analyse
manage
IMS
PA
T
Inst
rum
enta
l
Exp
ert
x=!
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Towards the PAT SoftwareTowards the PAT Software
• Concept elements• process as the main object• PAT solution as an output
“universal process modelling language”?• modular [open] toolkit
PAT platform• expert (model building) and operating (routine
application) level should be clearly separated• new principles of data handling
delivering the document on-line• “web-compatible”
remote information sources web-based solutions
• Software becomes a dominating part of the data analytical system
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PAT SolutionPAT Solution
• PAT company• software
development• linked to
hardware vendors
• scientific expetise
• independent
hardware
soft
war
e
serv
ice
science
Technical companies
Consulting companies
Software companies Academia
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Welcome to CollaborationWelcome to Collaboration
• Scientific expertise• experimental design• sampling• image analysis• new algorithms• uncertainty estimation
• Practical applications• industrial process control• environmental monitoring• quality control• …
• Joint development• PAT hardware• PAT software• integrated systems
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The endThe end
Thank you for attention!