ProCellics™ - RESOLUTION Spectra Systems · November 2016 ProCellics™ Bioprocess in-line Raman...
Transcript of ProCellics™ - RESOLUTION Spectra Systems · November 2016 ProCellics™ Bioprocess in-line Raman...
ProCellics™
Bioprocess in-line Raman Analyzer
ProCellics™ is the first Bioprocess Raman Analyzer for the biopharmaceutical industry fully dedicated to in-line
monitoring of the critical metabolites and nutrients during upstream processes, in order to maintain an optimal
development of mammalian cell culture in bioreactors. ProCellics™ measures the concentration of glucose, lactate,
glutamine, glutamate, ammonium, total cell density and viable cell density.
Thanks to ProCellics™, it is now possible to implement a GMP Process Analytical Technology solution for upstream
processes!
www.resolutionspectra.com
ProCellics™ Bioprocess in-line Raman Analyzer
What is Raman spectroscopy
ProCellics™ is based on Raman spectroscopy, an
optical vibrational spectroscopy technique consisting in
measuring the response of the molecular bonds to the
excitation by a laser. It provides in situ nondestructive
measurement with a very good selectivity, so that the
concentration of several essential compounds in the
complex culture medium can be monitored
simultaneously.
This technique has been recently validated by the
industry for cell culture monitoring and an outstanding
productivity improvement of fed-batches up to 30%
has been demonstrated.
Responding to the biopharmaceutical industry
unsatisfied needs
Better understand cell culture processes
Improve quality control of the final product by
implementing Quality by Design (QbD)
Enhance batch yield and prevent batch failure
Speed up process development, scale-up and
transfer to production
Fulfill regulatory requests
Solution benefits
Access to high-performance in-line monitoring of
metabolites and nutrients in the cell culture
Compact GMP design dedicated to bioreactors
environment for easy implementation
ProCellicsTM Soft provides a guidance to ease
chemometrics model building and Process Analytical
Technology monitoring with the software interfaces
and regulatory compliances required in the field
GMP hardware
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ProCellics™ Bioprocess in-line Raman Analyzer
ProCellics™ Soft
ProCellics™ Soft offers 4 modules providing guidance
for easy use.
The model building module includes:
A spectra sorting submodule: spectra affected by
bubbles or other disturbing events shall be
eliminated from model building. Each spectrum
can be easily linked with a reference measurement
A data pre-processing submodule to take into
account the analyzer calibration and to perform
spectra averaging and basic mathematical
operations
The monitoring module uses an integrated SIMCA
(powered by UMETRICSTM) engine (available in 2017).
Protocols Standards
Analyzer connectivity through an OPC® protocol CFR 21 part 11 compliance facilitated
SQL-database/ODBC protocol GAMP 5 development methodology
6m robust probe cable IP65
Compact design
providing flexibility
for its localization
Stainless steal tube and
sapphire window
Ethernet link
Interlock for laser safety
Immersion probe designed for CIP/SIP
and autoclave sterilization
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ProCellics™ key features
In-line real-time analytical sensing inside the
bioreactor
Measurement of the main metabolites and
nutrients concentration in the cell culture medium
Total and viable cell concentration measurement
GMP immersion probe of 12 mm diameter
adapted to PG 13.5 / M 18 bioreactor port
IP65 compact analyzer
Guidelines for chemometrics model building
Spectra sorting and preprocessing submodule
SQL-database / ODBC protocol
Connectivity through OPC® protocol
Interface with chemometrics software SIMCA (Powered
by UMETRICSTM)
Calibration procedure adapted to bioprocess
environment
ProCellics™ Bioprocess in-line Raman Analyzer
Glucose
Lactate
Ammonium
Glutamine
Glutamate
Other amino-acids
Total cell density (TCD)
Viable cell density (VCD)
Quantified metabolites and nutrients
Support and services
RESOLUTION Spectra Systems services offering will help you easily implement the ProCellics™ solution and get the
maximum out of it.
We offer support for installation of the hardware and software, training, validation and qualification (IQ, OQ, PQ),
maintenance services and an extensive email support. The software license includes the possibility to download the
most recent version. Our experts can also offer assistance for chemometrics model building.
Tests results: example of an assay involving a large number of cell cultures
ASSAYS Measurement range RMSEP # of factors
ANALYTES
Glucose 0 – 18.5 mM (0 – 3.33 g/L) 0.69 mM (0.12 g/L) 5
Lactate 4 – 34 mM (0.36 – 3.06 g/L) 1.19 mM (0.1 g/L) 5
Glutamine 0.5 – 3.35 mM (73 – 490 mg/L) 0.18 mM (26.3 mg/L) 4
Ammonium 0.15 – 2.57 mM (2.7 – 46.3 mg/L) 0.15 mM (2.7 mg/L) 3
CELL DENSITY/VIABILITY
TCD 1 – 16.5 x 105 cells/mL 0.97 x 105 cells/mL 3
VCD 0.8 – 12,3 x 105 cells/mL 0.9 x 105 cells/mL 5
ProCellics™ Bioprocess in-line Raman Analyzer
We conducted a pilot study on the monitoring of the main metabolites and cell density in a cell culture using
ProCellics™ with multivariate calibration. Fifteen replicates of a K562 cell culture in T175 flasks were sampled twice a
day for fourteen days. Raman spectra were collected, and the glucose, lactate, ammonium and glutamine contents
were obtained by enzymatic determination. VCD and TCD were measured using a cell counter. Pre-processing and
PLS modelling were applied to this dataset in order to build predictive models for each quantity of interest. The
resulting models account for the biological diversity present in the fifteen culture replicates. The obtained accuracy at
low analyte concentration is fully compatible with the needs of industrial bioprocess monitoring.
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ProCellics™ specifications
DISCLAIMER— The manufacturer reserves the right to change this
document at any time without notice and disclaims liability for
editorial, pictorial and typological errors. © 2016
RESOLUTION Spectra Systems SAS. All rights reserved.
RESOLUTION Spectra Systems
13 chemin du Vieux Chêne
38240 Meylan—FRANCE
Tel.: +33 4 58 00 12 49
www.resolutionspectra.com November 2016
ProCellics™ Bioprocess in-line Raman Analyzer
Culture type Mammalian cell culture
Monitoring In situ monitoring
Throughput 1 point / 15 minutes
Probe
Dimensions Ø 12 mm, length 220/420 mm
Port PG 13.5 / M 18, Cable gland
Cable length 6 m
Cleaning and sterilization Clean In Place / Steam In Place, Autoclavable
Laser
Safety Interlock , White Indicator
Power 500 mW
Analyzer
Interface Ethernet
Dimensions 37.5 x 33 x 7 cm (14.8’’ x 13’’ x 2.8’’)
Weight 5 kg
Standards CE, FCC, UL, RoHS
GMP, IP65