Nonclinical and Clinical Bioanalysis Using Ligand Binding Assays
In today’s fast-paced and highly regulated bioanalysis landscape, you no longer can rely on traditional methods for complex assay development. At Charles River, we go beyond conventional expectations by providing a comprehensive, end-to-end approach that proactively addresses the unique challenges of your therapeutic development. Our team’s deep expertise in developing and optimizing complex assays ensures that each step of the process—from reagent selection and binding optimization to stringent validation—is tailored to your specific needs in the drug development journey, from early discovery and candidate selection to late-stage clinical studies. When partnering with us, you can achieve:
Rapid Turnaround Times (TAT)
Accelerate your development timeline without sacrificing quality.
Proactive Troubleshooting and Risk Mitigation
Avoid costly setbacks with our anticipatory approach.
Comprehensive End-to-End Bioanalytical Services
Gain confidence in every phase of your therapeutic’s journey.
In a market where regulatory scrutiny and competition are at an all-time high, choosing a partner who understands these pressures and offers custom-built solutions is important. Our Ligand Binding Assays are not just services—they’re strategic assets designed to empower your program and de-risk your path to success, from preclinical phases through clinical milestones.
eGuide: Bioanalysis from Early-Stage to Clinical Drug Development
Accounting for modality complexity, evolving regulatory expectations, and the critical importance of upfront planning, this eGuide explains how to identify risks early and align your bioanalytical strategy with the needs of your compound, your timeline, and your team.
Learn More
Bioanalysis of Large Molecules to Support PK/TK Endpoints
In the current landscape of biologics development, the provision of selective and sensitive bioanalytical methods for the quantitation of the therapeutic candidate is critical to program success. Ligand Binding Assays (LBAs) are recognized as one of the most effective tools for delivering these methods.
Our extensive background in bioanalytical ligand binding assay testing services enables the provision of robust methods compliant with international regulatory standards, including ICH M10 guidelines. Leveraging our global scale and experience through our Global Laboratory Council (GLC) ensures we are able to handle even the most difficult and distinctive challenges that may arise during method development, validation, and execution in a regulated environment. Our various GLC sub teams meet on a regular basis to ensure regulatory and documentary alignment across the entirety of our global network.
Our team’s extensive experience in developing complex assays enables us to optimize each step of the process—from reagent selection and binding optimization to stringent validation— guaranteeing high precision, accuracy, and reproducibility. Our services offer solutions for effective analysis of a diverse array of products, including:
- Biotherapeutics
- Peptides
- Proteins
- Fusion proteins
- Monoclonal antibodies
- Oligonucleotides
At Charles River, we work with a variety of modalities every day, giving clients confidence in our experience and expertise. We see strong pull-through from non-clinical to clinical phases, enabling faster assay development and a smooth transition between stages. We keep processes harmonized across our sites to ensure consistent quality, and with our Apollo platform, clients can access bioanalytical data in real time for clear visibility and faster decisions."
Cara MaGuire, Associate Director, Clinical Bioanalysis LBA, Edinburgh, UK
Immunogenicity, Anti-Drug Antibody Support
Ligand binding assays play a vital role in the immunogenicity assessment required throughout the drug development process. Whether used as a tool to better understand PK or PD data in the nonclinical arena, or as a vital assessment of patient safety in the clinic our scientists have a vast amount of knowledge and experience to provide the anti-drug antibody (ADA) assays required.
Strong advocates for the leaner, fit-for-purpose approaches proposed in the nonclinical field, we offer tailored solutions based on immunogenicity risk and your preferred business strategy. From generic assays to support early candidate selection, through single-tier, screen-only methods, and finally titer or signal-to-noise measurement to provide insight into the magnitude of response, we offer full support throughout the drug discovery journey.
With many of our clients now looking to defer the decision on whether to proceed with ADA analysis until PK/PD findings has been evaluated, our SDS CUP_T tool offers full statistical interrogation of cut point data without the need of a dedicated statistician, expediting delivery of the method in addition to offering cost savings, thus enabling clients to take advantage of these flexible tools and strategies.
In the clinical arena, our assays evolve to meet the changing demands that may be encountered as the therapeutics progress through clinical trial phases. Our experts have a wealth of experience in the provision of methods to further characterize anti-drug antibodies findings, including the determination of neutralizing capabilities via cell-based or plates-based methodologies.
Webinar: The Critical Role of Bioanalysis in AAV Therapies
This webinar will explore the expanding role of bioanalysis in AAV therapies, focusing on biodistribution, transgene expression, immunogenicity, and ELISpot.
Watch Now
Biomarkers Analysis by Ligand Binding Assay
Identification of an informative biomarker is vital for successful drug development. Our knowledge and expertise with biomarker discovery services allows us to support you in the identification of a biologically and scientifically relevant biomarker.
Once a suitable biomarker has been identified, our experts ensure optimal assays are in place for measurement throughout the various stages of the drug development journey. Our experts propose fit-for-purpose validation adapted to the context of use (COU) for each biomarker.
In addition to bespoke assays to assess novel biomarkers, we offer an extensive library of validated biomarkers, such as cytokines, chemokines, and complement proteins. These existing methods can be leveraged across our global sites to support your studies.
Innovative Ligand Binding Assay Platforms
We leverage advanced technologies to address the complex needs of large molecule bioanalysis, ensuring accurate and reliable data for our clients. Each of these cutting-edge platforms provide unique benefits in sensitivity, reproducibility, and adaptability across a range of applications, including biomarker detection, pharmacokinetics, and immunogenicity assessments.
- Ultrasensitive Platforms (SMCxPRO / Quanterix)
- Ella
- Ligand Binding Assays with LC-MS detection
Integrated Ligand Binding Services
Our Ligand Binding Assay services span the entire drug development lifecycle, from discovery through clinical trials, providing clients with a streamlined and fully integrated solution. We offer:
- Assay Method Development, Transfer, and Qualification
Our expert scientists design tailored LBAs, selecting appropriate reagents and optimizing binding conditions to ensure reliable performance. - Method Validation
All assays are validated to meet global regulatory requirements, ensuring reproducibility, precision, and robustness for both nonclinical and clinical use. - Nonclinical and Clinical Sample Analysis and Management
Watson LIMS ensures full sample tracking from initial receipt to final disposal. With dedicated teams to manage both clinical and nonclinical receipt, we ensure rapid resolution of any discrepancies to allow timely delivery of data. - Apollo™ Data Management
Our Apollo platform enables real-time insights and instant access to your nonclinical bioanalytical data. - Regulatory Expertise
Our deep knowledge of global regulatory landscapes ensures that every LBA is developed and validated to meet international standards, supporting smooth submissions and compliance.
eGuide: Biomarker Solutions from Discovery to Clinical Trials
Learn how strategic biomarker integration can accelerate research & de-risk pipelines to bring life-saving therapies to patients faster. This guide helps you uncover smarter ways to de-risk studies and accelerate timelines, without compromising scientific rigor.
Read the Guide
Ready to Optimize Your Bioanalytical Strategy?
Our Ligand Binding Assay capabilities are designed to deliver high-quality data that accelerates your program and drives therapeutic success. Partner with us for expert guidance, rapid results, and bioanalytical services you can trust. Ready to discuss your specific bioanalytical needs? Whether you’re in the early stages of drug discovery or preparing for clinical trials, we have the capabilities and expertise to ensure your ligand binding assays are optimized for success. Reach out to our team of experts to learn how our tailored LBA services can help you achieve your milestones.
Benefits of Charles River Ligand Binding Assays
- Tailored Solutions to Meet Your Needs
- Expertise in Complex Modalities
- Accelerated Drug Development
- Real-Time Data Access and Management
Frequently Asked Questions (FAQs) About Ligand Binding Assays (LBAs)
-
How does a ligand binding assay work?
A ligand binding assay is used to quantify biotherapeutics and biomarkers and to detect anti-drug antibodies in biological matrices by measuring the interaction between two molecules or the binding of molecules to antibodies, receptors, and other large complex molecules.
-
What is considered a large molecule analyzed by ligand binding assays?
A large molecule or biologic is considered a protein having a therapeutic effect and most are complex and composed of more than 1,300 amino acids and are identical versions of human proteins. In today’s market we see increasingly innovative solutions with complex molecules such as ADCs, Oligonucleotides, and Gene therapies. These novel compounds often blur the lines when it comes to bioanalytical strategy with multiple techniques such as Mass Spectrometry or Q-PCR being used in addition to LBAs to fully answer the questions being asked.
-
What is the difference between ELISA and ECL technologies?
ELISA, or enzyme-linked immunosorbent assay, relies on enzymatic activity (e.g., HRP or horseradish peroxidase) to amplify the detection signal in a ligand binding assay. The technology is highly adaptable and relatively inexpensive as it does not require specific equipment beyond a standard microplate reader.
Electrochemiluminescence (ECL), which is used by MSD imager systems, is a principle based on the amplification of an electrical stimulus into light energy based on the quantity of a known ligand bound to an electrode. The advantage of ECL over ELISA is primarily the extended dynamic range which, in theory, is not limited, as well as the high selectivity for only the ligands bound to the electrode, which reduces interference of instrument noise.
-
Why is there a need to distinguish between nonclinical and clinical ADA assessments?
The presence of an antibody response against a therapeutic in the clinical environment is unwanted and steps are taken throughout the drug development process to minimize immunogenic potential. Despite these measures, the risk of a response remains and ADA assessments play an important role to play in monitoring patient safety. To satisfy this requirement, clinical ADA methods adopt a cautious multi-tiered approach to analysis. Each tier of the clinical method is designed to deliberately identify a small proportion of “false-positive" samples, minimizing the risk that any “true-positive” samples are missed.
In contrast, the presence of ADA in the nonclinical setting can be common. Many of the techniques utilized to minimize immunogenicity in humans will increase the likelihood of an ADA response in laboratory species. Most importantly, the presence of an ADA response in nonclinical studies is not predictive of events that will occur in the clinic. With the same safety concern not being present, ADA assessment instead becomes a tool to help understand findings in PK or PD data generated.
-
Why are anti-drug antibody assessments not quantitative?
When exposed to a novel therapeutic the immune response that may result will vary substantially, the population of antibodies raised against the therapeutic will often be very different even within individuals of the same species. As a result, a true reference standard like that used within a quantitative PK or TK assay will not be available. Instead, a surrogate positive control, typically a mAb or pAb generated in a non-human species, is employed. Using such a surrogate PC to provide a quantitative concentration of anti-drug antibodies would be scientifically flawed and potentially misleading.
Instead, statistically supported cut points are generated. These cut points act as thresholds to provide a qualitative positive or negative result for the sample on whether anti-drug antibodies are present.
On occasion, it may be useful for the investigator to understand the magnitude of the ADA response generated. In such cases, signal-to-noise ratios or titer values can be provided. However, it is recommended that investigators first consider the value of such additional data, as generation of these semi-quantitative results can be time consuming and costly.
-
How can biomarker testing services add value to my program?
Biomarker testing serves as a critical tool in drug discovery and development. The ability to develop biomarkers in animal models and translate them to the clinic can greatly accelerate candidate development as well as decrease associated risks and timelines.
-
What is a hybridization assay and when would it be used?
Hybridization assays are utilized for the measurement of RNA- or DNA-based therapeutics. Quantification is achieved using probes, complementary strands of nucleic acid, that enable capture and detection of the therapeutic. Hybridization assays come in a variety of formats including sandwich assays, where separate capture and detection probes complementary to a unique portion of the therapeutic are used, or cutting assays, where a single full-length probe is used to bind therapeutic present before an S1 nuclease is introduced to cleave any unbound probe preventing signal generation.