B2S Life Sciences has extensive expertise in the design, generation, characterization and life cycle management of custom, biological reagents. These custom reagents can be utilized to create robust assays for regulated bioanalysis to support evaluations of pharmacokinetics (PKs), toxicokinetic (TKs), immunogenicity of biotherapeutics and biomarkers.
Some of our unique critical reagent competencies include:
- Decades of experience in protein purification (antibodies, enzymes and other structural proteins) using variety of chromatographic techniques.
- Access to several unique biochemical and biophysical tools for detailed characterization of purified proteins and conjugates.
- Capability to generate conjugated (Biotin/Sulfo-Tag/Florescence-tag/ADC) proteins/peptides-Critical Reagents in small scale (≤1 mg) to scale-up production (≥ 100 mg) in sufficient quantity to avoid the need for producing new lots during In-study analysis of test samples
- Generation and characterization of anti-drug antibodies (ADA) positive controls in Rabbits/Chickens/Guinea Pigs etc.
- Capability to screen and purify preexisting human anti-drug antibody (ADA) positive controls from the serum of individuals who are seropositive (e.g. Purification of Gene Therapy vector, Adeno-Associated Virus (AAV) specific antibodies from seropositive human serum).
- Purification and characterization of Biomarker reference standard to support biomarker and CLIA assessments. Capability to scale critical reagent production in sufficient quantity to avoid the need for producing new lots during In-study analysis of test samples.
- Design, production and characterization of matched antibody pairs for optimization of PK/TK and quantitative biomarker assays.
- In-house generated custom Critical Reagents will be extensively biophysically and/or biochemically characterized for their intended use and a Reagent Characterization Form (RCF) will be available to the clients. The RCF includes but are not limited to the following: purity, concentration, label incorporation ratio, activity, titer, binding afﬁnity, specificity, isotype (monoclonal/polyclonal antibody), and aggregation propensity.
- Long-term storage of reagents in temperature-controlled environment (ambient, 4, -20, -80°C)
- ‘First-of-a-kind’ Inventory management tool (LCM+) to allow clients with on-line secure access to their reagent critical information.
- Periodic retest dates to ensure quality and updating of RCF.
- Support for reagent management and global distribution.
Our critical reagent design and development is a comprehensive technical collaboration between our experienced staff scientists and our out of lab partners. Our focus is always on mutual success, with a reagent strategy meticulously tailored to specific client needs. Under the supervision of a technical expert, clients can expect to be guided in the following sequence:
Assay Development and Qualification
Our Assay Development team designs and executes assays that complement our capabilities in custom critical reagents to enable our clients to efficiently make data-driven decisions for optimal analytical outcomes to support biotherapeutic drug development.
To realize this goal, B2S offers a range of services from drug discovery through nonclinical/clinical development. This includes early phase ADME investigations, reagent optimization, generation of optimal matched pair of antibodies, method qualification, and non-GLP sample analysis.
The range of bioanalytical methods includes assays to support PK/TK, detection and characterization of anti-drug antibody immunogenicity assays, assays to determination of novel biomarkers for assessments of pharmacodynamics.
These services include, but are not limited to:
- Reagent screening, binding kinetics, clone selection, Ab pair-selection, and epitope mapping/binning
- Quantitative method development
- Immunogenicity method development
- Competitive LBA Nab
- Cell-based Nab
- Flow-based assays
- Coated assay plate generation/development (i.e. ELISA, ECLIA, etc.)
- Critical Reagent Pack (Pharma-Grade Kit) development
- Chemistry, Manufacturing, and Controls (CMC) supporting assay development (e.g. Stability-indicating Drug Product Release Assay)
- Oversight of method transfer to a GLP contract research organization for sample analysis
- Exploratory and/or Non-GLP sample analysis
- Negative matrix pool screening
- Platform screening/conversion
- Drug Stability Comparisons (e.g. Buffer/Matrix half-life assessments of Drug Candidate(s)/Drug Products versus native endogenous molecule, precursors, and/or biosimilars
Additionally, we have access to high tech instrumentation and various testing platforms which include:
- BioTek® ELISA readers (Synergy H1™ and Synergy HT™) – UV-Vis, fluorescence, luminescence, etc.
- MSD® QuickPlex™ – Electrochemiluminescenct immunoassays (ECLIA)
- FortéBio OctetRED96™ and HTX™ instruments – Bio-Layer Interferometry (BLI) for label-free determination of binding kinetics, clone selection, epitope mapping/binning, and receptor binding
- Luminex® FLEXMAP 3D® – Multiplexing immunobead platform
- Beckman Coulter Navios Flow Cytometer – Cell-based/NAb assays
Cell Culture and Neutralizing Antibody Assays
At B2S Life Sciences we utilize cell culture in three major applications.
One application is the production of recombinant proteins in mammalian cells. In short, the cells are employed to produce critical reagents to meet the needs of our clients. Cell lines can be transiently or stably transfected to produce critical reagents, in order to insure a continuous supply. This allows us to provide consistent, high-quality products for our clients.
Initial steps include creation and/or scale-up production of expression constructs with DNA encoding target recombinant proteins. We can also produce AAV (Adeno-associated virus) in large scale to support gene therapy.
The second major use for our cell culture facilities is cell-based assays. The latter are performed in a separate facility that is dedicated for this purpose. Cell based assays include but are not limited to assessments for neutralizing antibodies (including those that neutralize SARS-CoV-2), cell viability, apoptosis/necrosis, proliferation and cytotoxicity, as well as immune cell isolation, separation and characterization, etc. Multi-parameter flow cytometry analysis is available for assessments of immune cell phenotype, activation, differentiation, and other functional testing.
The final major application is reagent development via phage display technology (performed in conjunction with Tango Biosciences). Formats available for biopanning for binders of clients’ targets include both scFv and monobodies formed from a human fibronectin type III scaffold. Affinity maturation via directed molecular evolution is also an option.
Biotherapeutic and CMC
Bioanalysis and CRO Management
At B2S Life Sciences we are proud to have expertise in multiple stages of drug development, including regulated bioanalysis and Contract Research Organization Management. Our expertise allows us to enable regulated bioanalysis by focusing our client support beyond conventional sample analysis. This strategy focus allows us to fill gaps that commonly exist to help ensure timely uninterrupted progress for achieving technical success. This novel business model makes B2S and an ideal partner for progressing projects from Discovery through clinical development. One example of our unique capabilities is that Regulated Bioanalysis and Contract Research Organization (CRO) Management Team who act as your agent to provide scientific oversight and project management to ensure CRO technical success.
Our team is equipped to help clients manage their projects in a multitude of scenarios. Our experienced scientists can collaborate with your team to create a specific development plan for efficient execution to assure steady progress to achieving your “a priori” defined milestones. Managing CROs and regulated bioanalysis is time consuming and requires experience and expertise for meeting regulatory expectations. To save time and money and meet your developmental objectives let the experienced B2S team of scientists handle your project. You will be glad you did!