Antibody Reagent Spotlight – Generating positive control antibodies for your Anti-Drug Antibody (ADA) assay

Biopharmaceuticals, including monoclonal antibodies, recombinant proteins, hormones, cytokines, growth factors, gene therapy products are a crucial class of therapeutic agents that have transformed the treatment of various diseases. As these complex molecules are introduced into patients, it is essential to monitor potential immunogenic responses. Biopharmaceuticals, including monoclonal antibodies, recombinant proteins, hormones, cytokines, growth factors, gene therapy products are a crucial class of therapeutic agents that have transformed the treatment of various diseases. As these complex molecules are introduced into patients, it is essential to monitor potential immunogenic responses. The potential immunogenicity of biological products results in the elicitation of anti-drug antibodies (ADA).  Anti-Drug Antibodies (ADAs) are immune responses generated against the therapeutic drug itself. The assessment of ADAs is a vital component of biopharmaceutical development. To ensure the reliability and sensitivity of ADA assays, positive control antibodies are generated as key reference materials.

The immunogenicity of a biotherapeutic is dependent on several factors such as protein aggregation, post translational modifications, protein folding, impurities in the formulation, route of administration, mode of action, patient population, treatment regimen and several other factors. The ADA response can potentially lead to allergic reactions and/or reduce or neutralize drug activity affecting drug exposure and thereby altering PK/PD profile. In some instances, this response may also result in hazardous cross-reactivity with endogenous proteins. This undesired immune response is an important safety concern for biopharmaceutical industry and regulatory authorities.

In view of these anticipated adversary effects of biotherapeutics, global regulatory authorities recommend that ADA responses be measured and evaluated from a safety perspective. The recommendation is a multi-tiered ADA testing paradigm which includes developing specific binding assays to detect all antibodies to the biotherapeutic drug. This approach involves a three-step process;

1. Initial rapid and sensitive screening assay to measure low and high affinity ADA
2. A confirmatory assay to establish that the detected ADA is specific to the biotherapeutic
3. Characterizing the ADA response by titration and neutralization assays

Positive control antibodies serve as a vital component of ADA assays. They are used to validate the performance of ADA assays. By having a known reference standard with known properties, assay accuracy, sensitivity, and precision can be determined and maintained. Positive control ADAs are essential for assay calibration, helping to establish standard curves and define the assay’s dynamic range, enabling the quantification of ADA levels. This is especially important in multi-center clinical trials where multiple laboratories are conducting ADA assays. Regulatory agencies such as the FDA and EMA require that screening and confirmatory assays achieve a sensitivity of at least 100 ng/mL of ADA in a given matrix for inclusion of positive control antibodies in ADA assays as part of the drug development process to ensure safety and efficacy.

Leveraging our experience in handling a broad range of antigen types, optimized immunization schedules & procedures, and the integration of various strategies, we are able to generate quality antibody reagents with much higher success rates, increased sensitivity and higher yields even against poor antigens such as oligonucleotide therapeutics.

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Need help generating anti-drug antibodies against your therapeutic for your ADA or PK assays?

Whether your project involves antibodies, recombinant proteins, hormones, cytokines, growth factors, gene therapy products or oligonucleotide antigens, contact us today to discuss your project needs.