Physicochemical and Biological Analytical Comparability for Biosimilars Complete Solution

Home , Ipilimumab, Natalizumab, Omalizumab

Industry Leader

Characterisation and comparability of biosimilar monoclonal antibodies

Expertise Speed to Market Greater Quality Assurance Industry leading experience Comprehensive range of Excellent regulatory and working with over 12 biosimilar off-the-shelf assays for industry insight for generating molecules and 30+ biosimilar biosimilar characterisation data required for regulatory developers and comparability to ensure submissions cost effective results

A unique range of integrated early stage development services to support biopharmaceutical drug development.

Cell Line Cell Bank Development Manufacturing

Complete Biosafety Testing Analytics Solution

Media

2 3 Experience

Sartorius offer a variety of methods to support the Currently, in our R&D pipeline we are developing testing of a wide range of biosimilar monoclonal methods to support assessments of biosimilarity for antibodies including: the following molecules:

Herceptin (trastuzumab) Actemra (tocilizumab) Humira (adalimumab) Synagis (palivizumab) --Enbrel (etanercept) --Eylea|Zaltrap (aflibercept) --Avastin (bevacizumab) --Xolair (omalizumab) --Lucentis (ranibizumab) --Orencia (abatacept) --Rituxan (rituximab) --Yervoy (ipilimumab) --Remicade (infliximab) --Tysabri (natalizumab) --Stelara (ustekinumab) -- --Simponi (golimumab) -- --Prolia (denosumab) --Actemra (tocilizumab)

“With 8% of our revenue invested in our R&D programme, we continually add to the molecules we support and extend the range of assays available for molecules already in our service portfolio”

4 Sartorius with clients throughout the biosimilar development pathway:

Cell Line Clone Process Product Comparability Commercialisation Development Selection Optimisation Characterisation

Our highly experienced team of scientists have developed methods for molecule characterisation, in line with regulatory requirements, allowing comprehensive analysis of a biosimilar to the originator molecule.

Complete Solution for Biosimilar Characterisation & Comparability

Structural & Physicochemical Binding activity Functional activity

Fab binding assays Fc binding assays ADCC CDC Functional bioassays

Molecular Target FcγRI Total PBMCs Rabbit Cell death weight binding by FcγIIa Lymphoid complement Cytokine --Charge --ELISA | --FcγIIb --enriched --Human --stimulation variants SPR | MSD --FcγIIIa(V | F) --PBMCs complement --Reporter --Carbohydrate --FcγIIIb Enriched NK -- bioassays structure --FcRn cells --Neutralisation --(glycans) --C1q --Reporter cells Peptide ------mapping -- --

5 Biosafety Testing

To complement our expertise in bioanalytical characterisation, BioOutsource by Sartorius also offers a suite of assays to assess the safety of biologics throughout the drug development pathway.

Our scientists have a wealth of knowledge and experience in biosafety testing, coupled with a thorough understanding of the regulatory requirements for biosimilar monoclonal antibodies and the cell lines used to manufacture these products.

Biosafety Tests

Microbiological Appearance & Viral safety testing Genetic analysis Other key assays contaminants Identity

Genetic Adventitious Sterility confirmation of cell Sequencing Endotoxin agents line identity

Mycoplasma In vitro assays Southern blot Abnormal toxicity

Residual impurities In vivo assays Gene copy number (DNA|HCP)

Retroviruses

FPERT

Infectivity assays

TEM

Species specific viruses

MAP & HAP

Bovine & Porcine

Real-time PCR

6 Cellca Cell Line Development

Cellca is a leading provider of Cell Line Development Services allowing customers easy, open access to a cost effective reliable technology platform. Cellca consistently delivers well characterised stable research clones from DNA to Research Cell Bank (RCB) in 14 weeks, with titres upwards of 3.0g/litre in an easily scalable fed batch process.

Key Components

CHO DG44 Chemically defined Growth in suspension Free of animal components --Long-term stability --Free of proteins & peptones Host Cell Media --Fully documented history --Optimised for Cellca cell lines -- Line System -- Key Components

DHFR system with high Expression Upstream Robust selection stringency Vector Process Easy to scale --Optimal signal peptide Design --Proven performance in --Freedom to operate --various bioreactor systems

Transfection & Pool Vector Cloning Single Cell Cloning Clone Evaluation RCB Preparation Generation

From DNA to RCB in 14 weeks

Cell Bank Manufacturing

The Sartorius service portfolio has been expanded and Key points to note: now offers fully cGMP compliant cell bank manufacturing. Closed, single-use manufacturing system with in line In order to mitigate risk and ensure the safety and quality of monitoring and control any biological product, it is essential to have a fully --Animal product free production characterised, well-documented, homogeneous master cell Up to 500 vial cell banks at 1-3×10⁷ cells per vial bank (MCB) and working cell bank (WCB). --Automatic vial filling system and controlled rate --cryopreservation We offer comprehensive biosafety testing services, --Storage of filled vials in vapor phase LN₂ including cell bank characterisation and genetic stability assessments of final producer cell lines. Contact-- our experts to discuss your cell bank manufacturing and cell bank characterisation requirements.

For further information please refer to the individual brochures for each service area.

7 Global Facilities

Glasgow, UK Göttingen, Germany Ulm, Germany Cambridge, USA Pangyo, South Korea

Germany USA Sartorius Stedim Biotech GmbH Sartorius Stedim North America Inc. August-Spindler-Strasse 11 565 Johnson Avenue 37079 Goettingen Bohemia, NY 11716 Phone +49 551 308 0 Toll-Free +1 800 368 7178

For further contacts, visit www.sartorius.com

Publication No.: S- -1534-e | Order No.: 85037-552-02 | Status: 09 | 06 | 2021