Immunogenicity testing is a critical component of the drug development process, particularly for products including biologics and cell and gene therapies.
Regulatory bodies like Health Canada and the FDA require comprehensive immunogenicity testing to safeguard patient safety and ensure therapies deliver their intended benefits.
However, conducting these assays in-house poses unique challenges—why is why pharmaceutical companies increasingly choose to outsource immunogenicity assay services to trusted laboratories. In the first of our four-part series, we will explore the main types of immunogenicity assays, why they are essential, and how to overcome the key challenges associated with each.
Let’s begin with anti-drug antibody (ADA) assays.
Anti-Drug Antibody (ADA) Assays
What Are ADA Assays?
Regulatory bodies like Health Canada and the FDA mandate ADA testing to identify immune reactions that could compromise patient safety or therapeutic outcomes.
ADA data is critical for characterizing the drug’s immunogenicity profile during clinical trials and post-market surveillance.
Key reasons include:
- Safety: ADA responses can cause hypersensitivity reactions, infusion-related reactions, or severe immune-mediated adverse events.
- Efficacy: ADA formation can reduce or negate therapeutic effects, particularly for biologics such as monoclonal antibodies, enzymes, or cytokines.
- Dosing Strategies: Understanding immunogenicity helps optimize dosing regimens to maintain therapeutic levels.
- Regulatory Compliance: ADA testing is integral to nonclinical and clinical immunogenicity assessments outlined in guidelines such as Health Canada’s “Guidance for Sponsors: Clinical and Nonclinical Requirements for Biologics” and FDA’s “Immunogenicity Assessment for Therapeutic Protein Products.”
How Are ADA Assays Conducted?
ADA assays typically involve a tiered testing approach to balance efficiency, sensitivity, and specificity:
- Screening Assay: Detects the presence of ADA using highly sensitive methods, often in a bridging ELISA format.
- Confirmatory Assay: Confirms the presence of ADA by demonstrating specificity, typically through competitive binding techniques.
- Titer Assay: Quantifies ADA levels to evaluate the magnitude of the immune response.
- Neutralization Assay (if applicable): Determines if ADAs neutralize the therapeutic’s activity, often using cell-based systems.
What Are Typical Challenges in ADA Assay Development and Execution?
ADA assay development is a highly specialized field due to the complexities involved in accurately detecting and quantifying ADAs.
Major challenges include:
Drug Interference: Masking Issues
High concentrations of the therapeutic in a patient’s sample can mask ADA detection, necessitating sophisticated techniques such as acid dissociation or precipitation.
Achieving Sensitivity Without False Positives
Balancing these parameters is critical to avoid false positives (detecting ADAs when none exist) or false negatives (missing ADAs that are present).
Matrix Effects: Serum Complexities
Patient serum or plasma contains various components that can interfere with assay performance, requiring robust controls and optimization.
Meeting Validation Requirements
Regulatory standards mandate rigorous assay validation to ensure reproducibility, accuracy, and robustness.
Why Conducting ADA Assays In-House Is Challenging
Setting up ADA testing in-house demands substantial investment in:
- Specialized Equipment: High-sensitivity platforms such as ELISA, ECL (electrochemiluminescence), or SPR (surface plasmon resonance) instruments.
- Expertise: Skilled immunologists and bioanalytical scientists are essential to develop, validate, and troubleshoot assays.
- Quality Standards: Compliance with Good Laboratory Practices (GLP) and other regulatory frameworks requires dedicated quality management systems
- Cost: The time and expense of establishing and maintaining capabilities can be prohibitive for most organizations
How We Can Help
Our bioanalytical lab specializes in ADA assay development, validation, and execution, offering comprehensive support to meet your regulatory and scientific needs. Why our customers trust us:
- Regulatory Expertise: Our team is well-versed in Health Canada, FDA, and EMA guidelines, ensuring your data satisfies global regulatory requirements.
- State-of-the-Art Platforms: We utilize advanced technologies such as Meso Scale Discovery (MSD) and Gyrolab® systems to deliver precise, reproducible results.
- Custom Assay Development: We tailor our ADA assays to your specific therapeutic, accounting for its unique structure, mechanism of action, and potential immunogenicity risks.
- Rapid Turnaround: With optimized workflows and dedicated project management, we deliver high-quality data on time and within budget
Partner With Us
By outsourcing ADA testing to Custom Biologics, you can focus on advancing your therapeutic pipeline while we handle the complexities of immunogenicity testing. We will help you streamline the immunogenicity assessment process, assist you in navigating the regulatory requirements efficiently, and help you bring your innovative therapies to market faster.
Let’s discuss how we can accelerate your drug development program. Reach out to our immunogenicity experts to discuss how we can tailor ADA assays for your drug development program.
