Our Solutions
Custom Reagents and Conjugation Chemistry
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, large bio molecule conjugates, viral particles/ nanoparticle etc.
- Capability to generate conjugated (Biotin/Sulfo-Tag/Florescence-tag/ADC) proteins/peptides/viral particles-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
- Capability to generate customized antibody conjugated magnetic beads to support immunocapture liquid chromatography mass spectrometry (IC-LC/MS) for regulated bioanalysis of ADCs [ Antibody Drug Conjugates] / Biomarkers etc.
- Generation and characterization of anti-drug antibodies (ADA) positive controls in Rabbits/Chickens/Guinea Pigs/llama 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:
Life Cycle Management
B2S provides LCM+ for Regulatory Compliant Storage and Tracking of Critical Reagents
With just a simple push of a button, our LCM+ portal provides global clients with instantaneous access to key information about your critical reagents! Our proprietary LCM+ service provides onsite storage of critical reagents in 24-7 temperature monitored freezer units. Portal access gives users the ability to track their samples in the B2S LIMS system, annual characterization information combined with defined retesting to ensure long term consistency. Moreover our portal enables Sponsors to make requests in real-time for shipping of their critical reagents to CROs or other destinations. Alternatively, CROs can initiate electronic requests for critical reagents and receive them upon Sponsor approval.
The LCM+ Portal will allow users to:
- Request reagents to be sent to your CRO labs and research partners
- Review quantities of available reagents
- Get comprehensive reports on your complete critical reagent portfolio in real-time
Assay Development & 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
- Early Discovery
- Antibody Titers
- Non-GLP method evaluation and sample analysis
- Quantitative method development
- PK/TK
- Biomarker
- Immunogenicity method development
- ADA
- 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
GLP Sample Analysis Lab Capabilities
The production lab at B2S Life Sciences has established itself as a GxP compliant lab and further enhances the support we can provide our clients. This lab is fully equipped to receive method transfers both internally and externally, validate methods, and support pre-clinical and clinical programs in support of regulatory filings.
The production lab handles quantitative PK/TK as well as fit for purpose biomarker methods that support regulatory filing. Additionally, the lab performs full and partial validations of ADA methods that include screening, confirmatory, titration, domain specificity, and neutralizing antibody assays.
B2S Life Sciences can validate method using a variety of platforms including Electrochemiluminescence, Colorimetric ELISA, Luminometric ELISA, and Luminex bead-based methods.
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.
Biomarker Assay Support
Today’s complex biotherapeutics and diverse treatment modalities rely heavily on biomarker assessments to provide key insights into pharmacodynamics (PK/PD), safety, efficacy, and disease related factors for optimizing decision-making.
B2S offers sponsors decades of experience for the development, validation and implementation of assays for novel biomarkers to support drug development and in vitro diagnostics. Our scientific team works with clients to devise bioanalytical context of use (COU) strategic plans for optimal decision-making. The B2S team’s biomarker experiences span different bioanalytical assay designs including quantitative assays, quasi-quantitative methods, and qualitative assays. In addition, our team is knowledgeable in the adaption of commercial assay kits for conducting biomarker assessments in support of nonclinical and clinical studies. In addition to conventional ligand binding assays, B2S can accommodate biomarker requests for varied technologies like LC-MS, flow cytometry, and molecular diagnostics.
Data Analytic and Writing Services
Statisticians and writers at B2S possess a wide range of experience with a variety of pharmaceutical companies. Collaborations between the statistics team, clinical scientists, data managers and writers allow us to generate high-quality data and interpretations in a timely fashion. Some key capabilities include:
Immunoassay Validation Statistics
- Develop study design and plate maps for running cut point experiments
- Create and review statistical and/or cut point sections of protocols, validation plans, and sample analysis plans
- Create and review analysis plans for cut point determination
- Calculation of cut points, sensitivity, MSR, projected LPC
- Population cut point comparisons
- In-study cut point determination
- Reagent bridging analysis
- Negative control pool selection and qualification study design
- Cross-validation study design and analysis
- CutPoint+ automated tool for development cut points
Clinical Immunogenicity Statistics
- Creation of analysis plans and table shells for clinical immunogenicity analysis
- Dataset specification development and review
- Analysis of clinical immunogenicity data
Consulting and Writing Support
- Statistical reports: Cut point and other method validation calculations
- Immunogenicity Risk Assessment: Preparation of risk assessment and immunogenicity strategy documents
- Clinical immunogenicity reports: Analysis and interpretation of immunogenicity data for inclusion in clinical study reports
- Integrated Summary of Immunogenicity: Create analysis plan, program outputs, write report or summary for inclusion in CTD
- Regulatory responses: Assist in answering questions from global regulatory authorities
Pharmacokinetics
PK/TK Data Analysis and Consulting Support
The applied science fields of pharmacokinetics, toxicokinetics, pharmacodynamics, clinical pharmacology, and bioanalytical sciences are inextricably connected and are core areas of expertise for our consultants. Successful development and commercialization of today’s biotechnology and conventional drugs requires the careful planning, execution, and analysis of a series of toxicology studies during preclinical evaluation and clinical pharmacology studies conducted in phase I to phase IV. Data from such investigations take a prominent place in product labeling, provide an underpinning for the mechanism of action, establish vital exposure-response relationships, and define dosing requirements in different populations. At the heart of all these studies are robust validated bioanalytical measurements of the drug substance in animal or human tissues and the application of state-of-the-art pharmacokinetic or pharmacodynamic analyses using specific models to assess and summarize the important findings. The efficiency of drug development can be increased by leveraging PK/PD analyses to understand complex dose-exposure-response time relationships.
Our consultants can help develop innovative strategies for implementing decisive studies that enhance the toxicological and clinical pharmacological evaluation of drugs leading to commercial success.
These services include:
- Non-GLP or GLP toxicokinetic evaluation for toxicology or ADME studies
- Phase I-IV PK study design and analysis
- Bioavailability and Bioequivalence design and evaluation
- Drug-Drug and Drug-Gene interactions
- Design and analysis of studies for special populations
Nonclinical and Clinical data PK and PD analyses supported
- Validated Phoenix WinNonlin® Compartmental and Noncompartmental models
- Exposure-dose-response relationships
- Accumulation and linearity assessment
- Individual animal or pooled data analyses – protocol specified analyses
- PK evaluation of phase I-IV clinical pharmacology and efficacy/safety studies
- Bioavailability, bioequivalence, drug interaction, and special population studies
Drug Development & Consulting Support
Drug Program Management – In House Drug development experts that lead programs from discovery to lead optimization and through clinical development
B2S Services Include:
- Developing non-clinical and clinical bioanalytical strategies supporting PK/TK and immunogenicity
- Drafting or reviewing bioanalytical methods for GLP and nonGLP studies
- Create assay and reagent Life Cycle management strategies to be consistent across programs
- Manage the development and implementation of a consistent and aligned assay strategy across programs
- Write and update immunogenicity risk assessments throughout drug development lifecycle
- Develop clinical phase appropriate and risk based statistical analysis plan for immunogenicity assessments
- Review PK and immunogenicity sections of Clinical Study Reports (CSR)
- General medical writing
- IND/BLA Plan and Submissions
- CRO Oversight
- Medical Writing
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!