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 • • PAT chemometrics software concept components making up a PAT solution

J&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

J&M Products

TIDAS II NIR

(1100 – 2100 nm) Integrated in-situ

Dissolution Test System

8-channel parallel

Chromatography System NOVA

fully-integrated Process Analyser

TIDAS

fully-integrated spectrometer for pharmaceutical applications

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

PAT players and driving forces quality& safety price

producer

profit, image

regulative organisation

quality& safety

consumer

LightHouse Probe

TM

(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

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 H 2 O is well established in-line technique

0 .4

0 .3

0 .2

0 .1

0 -0 .1

1 2 0 0 1 4 0 0 1 6 0 0 Wavelength (nm) 1 8 0 0 2 0 0 0

Case 1. Moisture monitoring (2)

r = 0.993

RMSECV = 0.58

a = 2 2 5 2 0 1 5 1 0 5 0 0 r = 0.996

RMSECV = 0.17

a = 1 (!) 1 0 2 0 3 0 4 0 5 0 time (min) 8 6 6 0 7 0 8 0 9 0 4 heating was interrupted 2 0 4 0 5 0 6 0 7 0 8 0

Case 2. Pellet Coating

• • • • • • Polymer coating of pellets for capsule filling PrecesionCoater TM • • 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?!

Case 2. Pellet Coating (2)

1 0 -1 3 SNV-corrected spectra 2 -2 1 2 0 0 1 4 0 0 1 6 0 0 Wavelength (nm) 1 8 0 0 RMSECV = 4.05

a = 3 2 0 0 0 1 1 8 0 1 1 6 0 1 1 4 0 1 1 2 0 1 1 0 0 0 3 .5

3 moisture 2 .5

2 1 .5

1 0 .5

0 0 1 2 2 0 5 0 particle size 1 2 0 0 5 0 RMSEP = 0.12

a = 2 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 1 0 0 1 5 0 time (min) 2 0 0 predicted deviation calibration sample 2 5 0 3 0 0

ProDicht Project

• • • 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

Additional wash tube Mirror Probe window Wash tubes Movable Tip

Technically, PAT is…

• • •

PAT = Hardware + Software

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

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, …

manage analyse

x=!

process acquire

Towards 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

PAT Solution

• PAT company • • • • software development linked to hardware vendors scientific expetise

independent Technical companies hardware science Consulting companies Software companies Academia

Welcome 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

The end

Thank you for attention!