Therapeutic Product Immunogenicity Community

Hi all,

Hope all is well!

I am looking for some advice/suggestion on the strategy to develop an ADA for multiple analytes. The drug product in development is a mixture of three hormones derived from human urine, and ADA is needed to monitor any potential immunogenicity. There are two options: 

1. Develop three ADA methods, one for each of hormone;
2. Develop a single method for the drug product, and later, if needed, further develop specific cut point for each analyte (similar to domain specific cut points). 

For the first option, we plan to label each individual hormone (using ECL bridging method), and PC will be individual PC for each hormone; for the second option, we plan to label the drug product and use PC that contains a mixture of three PCs. 

Has anyone had any experience on the 2nd option? Anything tricky to bear in mind during method development in terms of sensitivity and drug tolerance?

Thanks in advance!

Hi Jason,

I believe both options are viable. I would be inclined to do the 2nd approach, a little like how you would approach a multi-domain protein (in this case, a multi-component product) - first screen for ADA against the entire product, then look at domain/component specificity for positives samples.

For the component specifity, there are a few approaches, e.g.,

• compete with excess of each individual component (least sensitive, but easy to set up, as it is essentially an additional confirmatory assay for each component)
• compete with excess of each individual component, after immunodepletion of the other components (more sensitive than above, similar to the confirmatory again, but a bit more tricky to set up/run - see A novel approach to assess domain specificity of anti-drug antibodies to moxetumomab pasudotox, an immunotoxin with two functional domains - PubMed (nih.gov)
• use separate screening assays for domain/component specificity - this might be pretty easy to set up here as you'd simply (?!) remove the 2 other components/PCs from your screening assay

I would not expect drug tolerance to be an issue, levels of the cytokines are likely to be very low and clearance fast.

Regards,

Rob

Hi all,

Hope all is well!

I am looking for some advice/suggestion on the strategy to develop an ADA for multiple analytes. The drug product in development is a mixture of three hormones derived from human urine, and ADA is needed to monitor any potential immunogenicity. There are two options: 

1. Develop three ADA methods, one for each of hormone;
2. Develop a single method for the drug product, and later, if needed, further develop specific cut point for each analyte (similar to domain specific cut points). 

For the first option, we plan to label each individual hormone (using ECL bridging method), and PC will be individual PC for each hormone; for the second option, we plan to label the drug product and use PC that contains a mixture of three PCs. 

Has anyone had any experience on the 2nd option? Anything tricky to bear in mind during method development in terms of sensitivity and drug tolerance?

Thanks in advance!

I lean more to the first option, thinking of the blend as a fixed combination product. If the blend is 3 separate chemical entities, I would recommend 3 separate assays. That said, with smaller products, you may need to conjugate to a carrier for the method, in which case it starts to feel like it is reasonable to make the conjugates with all 3 at the same time. It might be more work to ensure consistent lots of critical reagents than to do 3 separate critical reagents, though.

Hi Jason,

I believe both options are viable. I would be inclined to do the 2nd approach, a little like how you would approach a multi-domain protein (in this case, a multi-component product) - first screen for ADA against the entire product, then look at domain/component specificity for positives samples.

For the component specifity, there are a few approaches, e.g.,

• compete with excess of each individual component (least sensitive, but easy to set up, as it is essentially an additional confirmatory assay for each component)
• compete with excess of each individual component, after immunodepletion of the other components (more sensitive than above, similar to the confirmatory again, but a bit more tricky to set up/run - see A novel approach to assess domain specificity of anti-drug antibodies to moxetumomab pasudotox, an immunotoxin with two functional domains - PubMed (nih.gov)
• use separate screening assays for domain/component specificity - this might be pretty easy to set up here as you'd simply (?!) remove the 2 other components/PCs from your screening assay

I would not expect drug tolerance to be an issue, levels of the cytokines are likely to be very low and clearance fast.

Regards,

Rob

Hi all,

Hope all is well!

I am looking for some advice/suggestion on the strategy to develop an ADA for multiple analytes. The drug product in development is a mixture of three hormones derived from human urine, and ADA is needed to monitor any potential immunogenicity. There are two options: 

1. Develop three ADA methods, one for each of hormone;
2. Develop a single method for the drug product, and later, if needed, further develop specific cut point for each analyte (similar to domain specific cut points). 

For the first option, we plan to label each individual hormone (using ECL bridging method), and PC will be individual PC for each hormone; for the second option, we plan to label the drug product and use PC that contains a mixture of three PCs. 

Has anyone had any experience on the 2nd option? Anything tricky to bear in mind during method development in terms of sensitivity and drug tolerance?

Thanks in advance!