CASE STUDY – DEVELOPMENT AND VALIDATION OF IMMUNOGENICITY ASSAYS FOR ADCs
Addressing ADC Regulatory Challenges by Providing Validated Assays for Multi-Domain Proteins
The FDA and EMA advised that the characterization of immune responses to protein products with multiple functional domains — including ADCs — may require multiple assays.
In response, the UK lab of Resolian has developed and validated assays in line with GCP/GLP standards, enabling analytical support throughout the full method lifecycle.
Challenges
In the development of antibody-drug conjugates, it is critical to understand the potential for immunogenicity. The FDA and EMA have stated that these responses must be characterized to determine their impact on the specific function of the drug domain. This presents a complex set of steps requiring multiple assay formats and domain-specific tools, complicating the development and validation process.
Not all CROs have the ability to develop and validate whole molecule and domain-specific assays for ADCs. For Resolian, however, this is an area of strength.
The Resolian Bioanalytics Solution
The Resolian UK Bioanalytics lab is comprised of elite method development, project management, and statistical teams. They have extensive experience developing immunogenicity assays for a broad range of multi-domain proteins, allowing them to deliver the right assay for each client’s individual needs.
The team have a proven track record of success using a tiered anti-drug antibody (ADA) approach:
- Screening ADC
- Anti-drug/linker ADAs use a molecular bridge to capture and detect antibodies to ADC
- Confirmatory ADC whole molecule assay
- Anti-Ab backbone and anti-drug/linker ADAs bind to unlabeled drug, reducing signal
- Confirmatory backbone-only assay
- Anti-Ab backbone ADAs bind to antibody backbone only, reducing signal
- Positive control
- Can be a pAb against the whole molecule or an mAbs mixture
This approach delivers validated immunogenicity assays that characterize immune responses to an ADC, supporting sample analysis throughout the method lifecycle.
Client benefits
The Resolian Bioanalytics development and validation approach gives clients the sensitive, specific, drug-tolerant immunogenicity assays they need to satisfy the stringent regulatory requirements for the approval of ADCs. This complex and rigorous process ensures that ADCs are safe and effective for patient use. Plus, knowing that they can confidently submit regulatory filings puts clients’ minds at ease.
DELIVERING VALIDATED ASSAYS FOR ADCS
Tiered approach to sample analysis
- Development and validation of multiple confirmatory assays
- Positive control can be a mixture of mAbs to different epitopes or a pAb raised against the whole molecule
Additional benefits
Not only do we ensure you have the right solution for their specific needs, but your validated assay also supports sample analysis throughout the method lifecycle.
Want to learn more?
Our team has considerable experience in the development of immunogenicity assays for a range of multi-domain proteins including; bispecifics, fusion proteins, antibody drug conjugates (ADCs) and modified (e.g. PEGylated) molecules.
We’re ready to discuss your project and answer any questions you have.
