GLP-Compliant MSD Assays for Immunogenicity Assessment of Biotherapeutics Across a Range of Species

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GLP-Compliant MSD Assays for Immunogenicity Assessment of Biotherapeutics Across a Range of Species

GLP-Compliant MSD Assays for Immunogenicity Assessment of Biotherapeutics

CELL & GENE | RNA | BIOLOGICS

Quantifying Immunogenicity with GxP-Compliant Precision.

The technical framework for GxP-compliant immunogenicity assessment using Meso Scale Discovery (MSD) electrochemiluminescence (ECL) assays is detailed here. We outline the application of these high-sensitivity assays for evaluating anti-drug antibody (ADA) responses to biotherapeutics, including AAV gene therapies and novel protein constructs, across multiple preclinical species. The discussion covers assay development, validation, and the strategic importance of robust immunogenicity data for IND-enabling programs, supported by insights from relevant scientific literature.

What is the typical sensitivity and dynamic range of your MSD immunogenicity assays?

Our MSD-based ADA assays typically achieve sensitivity in the low ng/mL range (e.g., 10-100 ng/mL), with a dynamic range spanning 3-4 logs. This performance is contingent on the positive control antibody and specific matrix, but the ECL platform consistently provides superior sensitivity over traditional ELISA for detecting low-affinity or low-titer ADAs.

How do you manage matrix effects from different species (e.g., rodent, NHP, human)?

We address matrix interference through a systematic assay development process. This includes screening for minimum required dilution (MRD), evaluating different blocking buffers, and testing various assay formats (e.g., bridging, direct binding). For complex matrices, we may implement sample pre-treatment steps, such as acid dissociation, to disrupt drug-ADA complexes and improve detection.

What is your standard approach for developing anti-drug antibody (ADA) assays?

Our approach follows a tiered strategy. We begin with a sensitive screening assay to identify potentially positive samples. All presumptive positive samples are then analyzed in a confirmatory assay that includes a drug competition step to verify specificity. For confirmed positive samples, we can proceed to characterization assays, such as isotyping or titer determination, and neutralizing antibody (NAb) assays.

Can you support both screening and confirmatory ADA assays under GxP?

Yes. All tiers of the immunogenicity assessment workflow, from initial screening to confirmatory and characterization assays, can be developed and validated to meet GxP requirements for regulatory submission. Our >100,000 sq ft facility is equipped to handle these studies, contributing to our clients’ IND-enabling programs.

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The Requirement for High-Sensitivity Immunogenicity Testing

Evaluating the immunogenic potential of a novel biotherapeutic is a core component of any preclinical safety program. An unwanted immune response, manifesting as anti-drug antibodies, can impact efficacy, alter pharmacokinetic profiles, or pose direct safety risks. Consequently, regulatory bodies require robust, validated methods for detecting ADAs in preclinical toxicology studies.

The MSD ECL platform provides a superior technological solution for this challenge. Its wide dynamic range and high sensitivity are well-suited for detecting low-titer ADA responses that might be missed by conventional colorimetric assays. This is particularly relevant for next-generation modalities where even a minor immune response can have significant biological consequences.

Watch the full-length video on DIVERSIFYING THE VALUE CHAIN

Cross-Species Immunogenicity: Bridging Preclinical Models to Human Outcomes

A central challenge in preclinical development is translating immunogenicity data from animal models to predict human clinical outcomes. Species-specific differences in immune recognition can lead to divergent responses to the same biotherapeutic, demanding assays capable of detecting subtle variations.

  • Vector-Host Interactions: Research into AAV vector engineering demonstrates that minor modifications to the capsid can alter biodistribution and host interactions. Studies show that species-specific differences in glycan presentation can predict how AAV variants bind to tissues in different models (PMID: 39001819). This highlights the need for bioanalytical methods that can accurately characterize immune responses across species to build a more predictive translational data package.

  • Translational Model Relevance: The value of selecting a relevant preclinical species is well-established. Work evaluating vaccine candidates has shown that robust humoral and cellular immune responses observed in non-human primate models provide strong rationale for advancing a program toward human trials (PMID: 12533717). This underscores the importance of generating high-quality immunogenicity data in the most appropriate species to de-risk clinical development.

A marketing flyer for Franklin Biolabs detailing their immunogenicity services, including various assays and support for cell and gene therapy clinical trials.

A scientist in a sterile laboratory setting uses a multichannel pipette to transfer pink liquid into a multi-well plate for a high-throughput experiment.

Franklin Biolabs’ GxP Bioanalytical Capabilities

Our bioanalytical team specializes in the development, validation, and execution of MSD-based immunogenicity assays within a GxP framework. We support programs from early discovery through IND-enabling toxicology studies, providing decision-making data on a timeline that aligns with accelerated development goals. Our integrated approach helps sponsors achieve a typical 18-24 month IND timeline. While the Franklin Biolabs brand was launched in 2024, our core scientific team has supported client programs with a 100% IND success rate since 2019.

Animal Welfare and the 3Rs

All in vivo studies are conducted through our strategic partners in AAALAC-accredited facilities under appropriate regulatory oversight. We are committed to the principles of the 3Rs (Replacement, Reduction, and Refinement). Our use of high-sensitivity assays allows for minimal sample volume requirements, contributing to the refinement and reduction of animal use in preclinical research.

Scientific Process Diagram

This content is for informational purposes. For guidance specific to your therapeutic program, please contact our team for a consultation.

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