Immunogenicity assays are an integral part of therapeutic protein and peptide development. Antibodies, recombinant proteins, and therapeutic peptides all have the potential to induce anti-drug antibody (ADA) responses, leading to reduced efficacy or induction of autoimmunity. CD Formulation has extensive experience in designing, validating, and optimizing antibody immunogenicity assays in compliance with FDA regulatory and safety guidance. We offer a wide range of immunogenicity testing services to detect anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) to support non-clinical research worldwide.

What is Immunogenicity?

Immunogenicity refers to the ability of a substance to be recognized as a foreign invading substance and to cause the body's immune system to produce a specific immune response. For biopharmaceuticals, such as recombinant proteins, therapeutic peptides, and antibody-drug conjugates, given their defense mechanism, the human immune system may label these macromolecules as foreign invaders and initiate subsequent reactions, thereby affecting the efficacy and safety of the drug. Immunogenicity assays provide a way to measure potential immune responses to biopharmaceuticals and biosimilars. Typically, a single biologic requires a panel of assays to gain a complete understanding of potential immunogenicity. FDA stipulates that assays should be designed to provide adequate sensitivity, be free from confounding interference, consider potential risk, and detect physiological consequences, thus predictive data can be collected about the strength and type of immune response a drug is likely to produce in humans.

Fig. 1 Simplified schematic of T cell-mediated immune response to a therapeutic protein. (Rosenberg AS, et al., 2018)

Explore Our Proteins & Peptides Immunogenicity Assay Services

Immunogenicity assays are complex and can be extremely challenging due to interactions and interferences between the drug, target, and sample matrix. Therefore, careful selection of assay formats is crucial for further optimization and validation.

To design, develop, and validate robust immunogenicity assays, CD Formulation senior scientists use a multi-layer screening approach to measure anti-drug antibodies (ADAs) and neutralizing antibody NAbs to assess the immunogenicity of therapeutic proteins and peptides, thereby helping our clients obtain rigorous data.

Thanks to extensive expertise in quantitative analysis of multiple therapeutic proteins and peptides. Our immunogenicity analysis laboratory continues to grow and assist our customers in the following areas, including:

• Validation of ADA screening, validation, and characterization assays, involves qualitative and quantitative determinations using a multilayered approach.
• Development of direct or bridged ELISA, direct or bridged ECL assays.
• Characterization of ADA in titer and neutralization assays.
• Develop drug tolerance assay method by using acid dissociation MSD Bridging Mastermix, ECL/ELISA-based acid dissociation solid phase extraction (SPEAD), affinity capture elution (ACE), nanoparticles or magnetic beads, etc.
• Integration of pharmacokinetic (PK) from in vivo studies and immunogenicity results.

General Workflow

Our scientists systematically develop methods for high-quality and reproducible antibody immunogenicity assays. Typically, we support clients in developing screening methods to measure immunogenicity. ADA titer determination and confirmatory assays were subsequently performed. We also help develop custom antibody immunogenicity assays by examining the risk or safety of the antibody and the intended use of the drug, including:

• Screening assays to detect anti-drug antibodies (ADA) that bind to a therapeutic protein or peptide biopharmaceuticals. The assay typically uses a ligand binding assay (usually an ELISA or MSD) with a labeled drug for capture and detection.
• The magnitude of anti-drug antibodies (ADA) in confirmed positive samples is then characterized by titer determination.
• The neutralizing capacity of ADA in samples confirmed positive is then characterized to reflect the drug's mode of action, including cell-based assays or competitive ligand binding assays.
• Immunogenicity assessment of NAb activity is also performed using cell-based assays or competitive ligand binding assays (LBA).
• In some cases, we will further characterize, such as assessing cross-reactivity with endogenous antigens, domain specificity of multi-domain products, or isotyping of ADA.

Why Choose Us for Proteins & Peptides Immunogenicity Assay?

• We have extensive experience and expertise in developing therapeutic protein and peptide immunogenicity programs.
• We understand the critical nature of ADA analysis in non-clinical and clinical trials or NAb assay development projects.
• Our responsive and flexible immunoassay bioanalytical laboratories for ADA analysis and NAb determination will greatly accelerate your drug development process.
• Successful experience with hundreds of therapeutic protein and peptide immunoassay projects.
• Custom ADA assay development and cell-based nAb assay development services lab.
• Customized immunogenicity testing methods for ADA and Nab assays with cut-point analysis and drug or antigen interference.

Publication

CD Formulation has extensive knowledge in developing therapeutic protein and peptide immunogenicity programs. Our scientists will work closely with you to ensure your assay is properly developed and validated and meets all regulatory requirements. Please feel free to contact our team to learn how we can help you achieve your immunogenicity testing goals throughout your product’s development lifecycle.