ProCellics. In-Line & Real-Time Bioprocess Raman Analyzer

Transcription

1

2 ProCellics is the first GMP Bioprocess Raman Analyzer for the biopharmaceutical industry fully dedicated to in-line monitoring of the critical parameters and quality attributes in real-time, in order to maintain an optimal development of cultures in bioreactors and to better control downstream processes. ProCellics measures among others the concentration of glucose, lactate, ammonium, glutamine, glutamate, other amino acids, proteins, Total Cell Density and Viable Cell Density. Thanks to ProCellics, it is now possible to easily implement a GMP Process Analytical Technology solution for upstream and downstream processes! Solution benefits Better understanding of bioprocesses Improving quality control of the final product by implementing Quality by Design (QbD) Enhancing batch yield and preventing batch failure Speeding up process development, scale-up and transfer to production Fulfilling regulatory requests Solution advantages Access to high-performance in-line monitoring of key process parameters in the cell culture Compact GMP design dedicated to bioprocess environments for an easy implementation ProCellics TM Software provides a guidance to ease chemometric model building and Process Analytical Technology monitoring, with the software interfaces and regulatory compliances required in the field 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 complex media 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. 1

3 GMP hardware Ethernet link CE, FCC, RoHs IP65 6 m robust probe cable Compact design providing flexibility for its localization Laser safety (IEC): interlock, key control... Stainless steel tube 12mm, length 220/420 mm PG 13.5/M18, Cable gland Immersion probe designed for CIP/SIP and autoclave sterilization Laser spot ~300 mw Working distance 0.3 mm from sapphire window ProCellics Software ProCellics Software offers 4 modules providing guidance for an 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 A reference association submodule: 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 BioPAT SIMCA (powered by Sartorius) engine. Protocols Analyzer connectivity through an OPC server Standards CFR 21 part 11 compliance facilitated SQL-database 2

4 ProCellics key features In-line analytical monitoring inside the bioreactor Real-time display/opc transfer of quantified parameters Easy multivariate calibration with ProCellics Software / SIMCA GMP immersion probe of 12 mm diameter adapted to PG 13.5 / M 18 bioreactor ports CFR 21 part 11 facilitated Measurement of the main metabolite and nutrient concentrations in the culture medium Total and viable cell concentration measurement Protein titer and other key parameters measurement IP65 compact analyzer SQL-database managed by ProCellics Software Connectivity through OPC server Calibration procedure adapted to bioprocess environments Quantified parameters Glucose Lactate Ammonium Glutamine Glutamate Other amino acids Proteins Total cell density (TCD) Viable cell density (VCD) Support and services RESOLUTION Spectra Systems service 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 (IQ/OQ), training and maintenance services. In order to guarantee a fast implementation of ProCellics, our experts can offer support for the first set up including multivariate calibration and first monitored batches. 3

5 Tests results: example of a CHO cell culture monitoring These results come from a pilot study on the monitoring of the cell density and the main metabolites in a cell culture performed in a 5L bioreactor and using ProCellics for in-line measurement. The real-time quantitation of the critical parameters with ProCellics is based on multivariate calibration models processed from the data acquired during four calibration batches with important variabilities and including spikes of glucose and glutamine. This represents a total of 67 reference data points. Off-line measurements, both for multivariate calibration and for comparison in the following graphs, have been performed with a Nova Flex2 off-line analyzer. The obtained accuracy is fully compatible with the needs of industrial bioprocess monitoring. ANALYTES Range RMSEcv* # of factors Glucose g/l 0.34 g/l 4 Lactate 0 52 mm 1.7 mm 5 Glutamine mm 0.76 mm 6 Ammonium mm 0.44 mm 4 Glutamate mm 0.09 mm 4 CELL DENSITIES TCD x10 5 cells/ml 1.71 x 10 5 cells/ml 6 VCD x10 5 cells/ml 1.41 x 10 5 cells/ml 5 Example of results for a CHO cell culture *RMS Error of cross-validation 4

6 ProCellics specifications Culture type Monitoring Throughput Mammalian cell culture / fermentation / downstream In situ monitoring of main nutrients, metabolites, cell densities and other key parameters 1 point / 5-15 minutes Probe Dimensions Port Cable length Cleaning and sterilization 12 mm, length 220 / 420 mm PG 13.5 / M 18, Cable gland 6 m Clean In Place / Steam In Place Autoclavable Laser Safety Power Interlock, White Indicator 500 mw Analyzer Interface Ethernet Dimensions 37.5 x 33 x 7 cm (14.8 x 13 x 2.8 ) Weight Standards 6 kg CE, FCC, UL, RoHS GMP, IP65 RESOLUTION Spectra Systems 13 chemin du Vieux Chêne Meylan FRANCE Tel.: info@resolutionspectra.com DISCLAIMER The manufacturer reserves the right to change this document at any time without notice and disclaims liability for editorial, pictorial and typological errors RESOLUTION Spectra Systems SAS. All rights reserved. November 2017