Customized Biomaterials

OEM

Customized Biomaterials Development & Manufacturing

Living ImmunoassayExcellence

2 Customized Biomaterials. Development & Manufacturing

Werfen is a growing, family-owned, innovative company founded in 1966 in Barcelona, Spain. Our OEM Technology Center has consolidated experience in research, development and manufacturing of customized assays and biomaterials. We offer end-to-end solutions for the IVD industry with the most innovative capabilities to enhance competitiveness and time-to-market.

Our mission is to become your partner of choice as a center of excellence in providing innovative end-to-end OEM solutions (products & services) to IVD companies.

Innovation

Our OEM Technology Center ranks among the top centers of excellence for immunoassay and biomaterial development and manufacturing in the industry. Our focus on technological advances ensures our customers access to state-of-the-art R&D and manufacturing capabilities. Werfen’s innovative nature is strengthened through close relationships with prestigious universities and biotechnology research centers around the world.

Operational Excellence

Our key strength is the combination of the ongoing effort to improve our organizational processes, products and services with the Werfen mindset that embraces principles and tools to create a sustainable partnership with our customers and employees.Our Quality System is certified to ISO 13485:2016 / EN ISO 13485:2016 as well as MDSAP.

Commitment

Customers and patients benefit from the efficiency of a talented global team of qualified and specialized professionals who lend their enthusiasm, dedication and energy on a daily basis in order to provide high quality products & services.


You can rely on the expertise and capabilities of our R&D and Operations

teams to develop and manufacture customized Biomaterials

> 200 Biomaterials

developed

> 10 differentclinical fields

Use on commercial WW assays


DesignBased on your needs we can design the entire process for generating a new recombinant antibody.

If you already have an antibody in mind, we can modify it to meet your needs: improving affinity, sequence modification, tag addition, etc. Our expertise in recombinant antibodies extends to different antibody formats. If your needs are related to a specific antigen, we can also design the entire generation and production process for this new recombinant antigen or we can modify an existing one by improving affinity, sequence modification, tag addition, improving stability, among others. In addition, we have in-house bioinformatics protein modelling to simulate how the biomateiral could be affected in different conditions.

One of the major challenges for an IVD company is to obtain IgM-positive plasma and serum to be used as controls or calibrators for diagnostic assays since IgMs have a short life, disappearing earlier than IgGs. In order to overcome this challenge, our customized biomaterials team has developed a process to generate a recombinant IgM antibody that can be used as a calibrator or control for a diagnostic assay.

Figure 1. Summary of the process of generating an IgM antibody to be used as a calibrator or control


ScreeningIn this step of the process, the most appropriate expression systems are screened based on production yield, protein performance, stability, binding kinetics and cell viability.

At the end of the screening step we can select the ideal strain/clone that would produce the biomaterial that will best meet your needs.

Figure 1. Summary of the process of generating an IgM antibody to be used as a calibrator or control

Our current R&D expertise and our current operations use the following biomaterial sources to produce the biomaterials needed to supply assays covering a wide range of clinical fields to customers worldwide.

Microbial strains:

Recombinant antigens

Hybridomacell lines:

Monoclonal antibodies against

viral & human antigens

Mammaliancell lines:

Viral & human antigens

Baculovirus expression systems:

Viral & human antigens

Native: Viral, human

& mammalian antigens.

Polyclonal antibodies

Yeast:Recombinant antibodies &

antigens


Purification & Characterization Our extraction & purification platforms are optimized taking in consideration that the purified antibody/protein will be used in a diagnostic assay. Based on your needs, we can perform peptide mapping analysis, evaluate state of aggregation, as well as determining your sample molecular weight distribution, purity, charge variants and glycosylation patterns among others.

Figure 2. Example of Peptide Mapping (PEM).

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uVrIgG + tagrIgG Hybridoma IgG


The characterization process of bioma-terials to be used in diagnostic products is key to understanding and managing posttranslational modification variants, along with process and product related impurities. This approach is crucial for product con-sistency and quality. One of our customers requested that our customized biomaterials team characterize a full IgG antibody from hybridoma, and a new recombinant IgG antibody (designed as an alternative for the full IgG antibody from hybridoma). As you can see in Figure 2, the peptide mapping done by our customized biomaterials team ensured that both the hybridoma and recombinant IgG molecules ultimately presented a similar tryptic profile.

During the process of producing an antibody, the glycosylation pattern must be understood in order to assess the performance and reproducibility of the selected antibody. Our biomaterials team did the analysis of the glycosylation pattern (Figure 3) of a full IgG monoclonal antibody and a F(ab’)2 fragment from the same hybridoma. The objective of this analysis was to optimize the cell culture and the purification conditions of that monoclonal antibody and its F(ab’)2 fragment.

Figure 3. Example of Hydrophilic Interaction Chromatography (HILIC) to assess glycosylation pattern.

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Moreover, functional tests for the requested biomaterial can be provided. These tests include affinity constants and interaction kinetics by biolayer interferogram and surface plasmon resonance as well as diagnostic assays.

Apart from Bio-Layer interferometry and surface plasmon resonance, our biomaterials can benefit from R&D assay development to assess the functionality of a new biomaterial in latex based or chemiluminiscence based immunoassays.


Process Optimization& Scale-up

The strategy for process scale up is selected based on your operational demands. When scaling up, an optimization process is needed in order to improve productivity and streamline supply chain operations.

When facing a production process optimization and scale-up, our biomaterials team (a co-team of biotecnhology R&D and Manufacturing) takes into consideration the improvement of the protein or antibody expression system and optimization of the culture conditions to increase the specific production of the biomaterial for diagnostics.

Once the production process is optimized it can be scaled up to the optimal production system such as a bioreactor up to 100L.


Figure 4. Example of a manufacturing processs optimization and scale-up: In the graph on left Size Exclusion Chromatogra-phy for the analysis of the recombinant antigens obtained with curent and optimized manufacturing proceprocess and a elec-tronic microscopy image of the recombiant antigens obtained after the manufacturing process optimization and scale-up.

Our biomaterials team works towards the goal of streamlining biomaterials production so as to optimize and scale up the production process for a biomaterial for diagnostics. In figure 4 you can see a couple of examples of the results obtained after the manufacturing process optimization and scale-up to bioreactior of a recombinant viral antigen (virus like particles) to be used for a diagnostic assay to detect antibodies.

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Optimized manufacturing process for recombinant AntigenCurrent manufacturing process for recombinant AntigenInjection


ManufacturingWerfen’s state-of-the-art production facilities can adapt to your supply needs thanks to their capabilities:

We have the biomaterial supply chain integrated in the same building, this allows us to being able to secure the supply to our partners. Note that in the midst of the 2020 WW health crisis, during the first half of the year we were able to supply more than 20 different Biomaterial references to more than 15 different IVD companies located worldwide.

35,000 m2 (376,736 ft2) facilities, including 9,200 m2 (99,000 ft2) dedicated to production activities

State-of-the-art equipment: Bioreactors, AKTA Systems among others

More than 200 product dedicated purification columns

Positive-and negative-pressure laboratories

Biosafety level 2 laboratories

Production under GMP procedures

Final QC, physicochemical and functional analysis


With Werfen’s CustomizedBiomaterials you can get access to

Downstream Capabilities

Biomaterial Sources In-Process Controls

MonoclonalAntibodies

Hybridorna Cell Lines

Mammalian cell lines (recAb)

PolyclonalAntibodies

Goat

Rabbit

Guinea Pig

RecombinantProteins

Microbial Strains

Mammalian Cell Lines

Baculovirus Expression System

Yeast

Viable and total cells concentration by automatic cell counter

Nutrients and byproducts analysis

Cell populationanalysis

Cell culture aminoacid analysis

Protein Purification

Protein Extraction

Centrifugation & Ultracentrifugation

Microfiltration & Ultrafiltration

Chromatography (Affinity, IEX, SEC, HIC, Multimodal)

Protein refolding

Chemical modification

Labeling

Protein Characterization

Physicochemical Analysis

UV Spectrophotometry

Electrophoresis

Isoelectric point determination

Ion exchange chromatography

Glycosytation pattern

Peptide mapping

Protein amino acid analysis

Surface hydrophobicity

DSF (differential scanning fluorimetry)

Functional Analysis

Surface plasmon resonance

Bio-Layer Interferometry

Enzyme-Linked Immunosorbent Assay (ELISA)

Chemilluminescent Immunoassay

Latex based immunoassay

NativeAntigens

Bacteria

Viruses

Human Sera

Upstream Capabilities


Thanks to our collaborations with innovative companies, academic institutions and research centers, the following techniques are available to characterize your biomaterial of interest.

Our facilities are located in Llicà d’Amunt, Barcelona and cover more than 35,000 m2 (376,736 ft2). Contact us at [email protected] to discuss your customized Biomaterial needs and request a call back.

Functional Analysis

Surface plasmon resonance

Bio-Layer Interferometry

Enzyme-Linked Immunosorbent Assay (ELISA)

Chemilluminescent Immunoassay

Latex based immunoassay

MassSpectrometry

Protein & DNA sequencing

Higher Order structure analysis (Circulardichroism & IR spectrophotometry)

ElectronMicroscopy

PeptideSynthesis

Epitopemapping

Differential Scanning Calorimetry

3100

-980

3 R0

1 SE

PTEM

BER-

2021

Can Malé08186 Lliçà d’AmuntBarcelona, SpainPhone: +34-93-860-9000werfen.com/oem

Living ImmunoassayExcellence

Customized Biomaterials

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