Using an ADA Assay with MSD for High-Throughput Immunogenicity Studies

With a rising demand for biologic drug development, high-throughput immunogenicity assessments are becoming increasingly critical. These demands necessitated established analytical platforms for a comprehensive assessment of immune responses across diverse study samples. Meso Scale Discovery assays are one such robust platform developed for efficient immunogenicity testing.

Meso Scale Discovery multiplex technology is a pioneer of the electrochemiluminescence platform for immunogenicity testing. It combines superior sensitivity with multiplex abilities. Today, Mesoscale ELISA has emerged as a gold standard tool for ADA detection, offering reduced sample requirements and enhanced throughput compared to traditional methods. Not to mention, automated processing and innovative detection technology are analytical advantages of Meso Scale Discovery assays for advancing immunogenicity research. The current article explores Meso Scale Discovery multiplex and singleplex assay systems for high-throughput immunogenicity studies.

MSD technology fundamentals for immunogenicity assessment

Immunogenicity assessments are critical for biopharmaceutical development. Most importantly, regulatory agencies such as the US FDA have strict guidelines for immunogenicity testing. Hence, these stringent regulations around ADA assay development and validation require more tolerant and robust methods. Due to its larger dynamic range, increased sensitivity, and higher therapeutic tolerance, MSD Mesoscale assays have gained prominence for ADA testing. MSD analysis supports each stage of immunogenicity assessments through:

• Exceptional inter- and intra-assay precision
• Superior sensitivity
• Minimal matrix effects
• High drug tolerance
• Flexible platform
• Broad dynamic range

MSD has a portfolio of assay development reagents, plates, and kits for all stages of biotherapeutic drug development. They are rigorously tested for precision and reproducibility to demonstrate exceptional inter- and intra-lot consistency. MSD product line includes:

• MSD gold sulfo-tag conjugates: stable and easy to prepare conjugates for sensitive detection
• MSD gold Streptavidin plates: industry standard plates for consistency, performance, and convenience
• U-Plex development and ELISA conversion pack: comprehensive development tools for custom-designed immunoassays

MSD also offers services to cater to challenging immunogenicity testing, including neutralizing antibody assays, custom assay plates, and drug reagents or conjugated antibodies. Moreover, these services include:

• Assay development: Experienced MSD scientists offering high-quality ADA assays for immunogenicity applications
• Conjugation: leverage knowledge and expertise in manufacturing for conjugating biomolecules with Sulfo-tag labels or biotin for ADA studies
• Prototype printing: custom-designed MSD assay and plates printed with agents of choice

Multiplex capabilities and high-throughput applications

Meso Scale Discovery Multiplex assays are a revolutionary technology for immunogenicity assessments. It simultaneously detects multiple analytes with precision and efficiency. A comprehensive MSD multiplex analysis includes screening, confirming, and detecting the neutralizing ability of ADAs. Due to its multiplexing capacities, MSD reduces sample requirements, provides an effective strategy, and increases high throughput for extensive immunogenicity studies. These unique advantages make MSD multiplex assays more convenient than traditional ELISA assays, as they overcome several limitations of these conventional assay systems.

MSD multiplex systems offer custom panel development for therapeutic applications with the flexibility to accommodate several analytical requirements. These customized solutions, combined with high-throughput capabilities, are ideal for population-based immunogenicity testing and large-scale clinical studies. These unique characteristics of MSD analysis are helping drug developers transform immunogenicity testing through reduced costs, enhanced efficiency, and comprehensive analytical coverage.

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ADA assay development and validation

ADA assay development using MSD technology employs a systematic approach emphasizing the exploitation of the unique properties of the platform for adequate immunogenicity assay development and validation. The US FDA guidelines recommend using a multi-tiered approach for immunogenicity testing. This approach is ideal for managing large-scale immunogenicity testing recommended for biotherapeutic drug development. A multi-tiered approach to ADA mesoscale analysis includes screening, confirmatory, and neutralizing antibody assays. The initial ADA screening assay should be sensitive enough to detect anti-drug antibodies present at low levels. Positive samples are then tested via confirmatory assays to remove false-positive results. Finally, anti-drug antibodies are characterized through cell-based neutralizing assays to determine their capacity to neutralize biotherapeutics.

MSD assays support regulatory development and validation requirements through superior accuracy, reproducibility, and precision. Besides, its higher drug tolerance feature enhances its capacity to evaluate ADAs in the presence of biotherapeutics. However, utmost care is necessary for reference standards, quality control measures, and method validation to ensure reliable and accurate immunogenicity results. MSD offers automation capacities to support high-throughput studies and minimize potential variability due to manual handling. These unique features of MSD assays enable robust assay development and validation to support clinical implementation and regulatory requirements.

The road ahead for Meso Scale Discovery assays in immunogenicity testing

The fundamental advantages of MSD technology are its superiority as a platform to conduct high-throughput immunogenicity studies. Immunogenicity is a significant challenge faced while developing biotherapeutic proteins and large biomolecules. A robust and reliable tool is necessary for accurate immunogenicity testing. Meso Scale Discovery assays have emerged as a reliable method for advancing immunogenicity testing and supporting Drug Development programs. They offer multiplex technologies to provide a comprehensive evaluation of immune responses. Understanding the potential of MSD technology in deciphering immunogenic responses will be critical in supporting biologic drug development and accelerating developmental timelines.