ProCellics™ - RESOLUTION Spectra Systems · November 2016 ProCellics™ Bioprocess in-line Raman Analyzer Culture type Mammalian cell culture Monitoring In situ monitoring Throughput

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



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


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


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


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.


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

[email protected]

www.resolutionspectra.com November 2016


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

Documents

ProCellics™ - RESOLUTION Spectra Systems · November 2016 ProCellics™ Bioprocess in-line Raman Analyzer Culture type Mammalian cell culture Monitoring In situ monitoring Throughput