Bioanalytical Community

Hi everyone,

I've been exploring this topic within my organization and wanted to gather broader insights. From my current understanding, and that of my bioanalytical colleagues, the drug tolerance from the screening assay is typically used to determine the presence of inconclusive samples. I have been recently on discussions whether drug tolerance from confirmatory assays, nAb, and other characterization tiers should be considered as well.

To better understand industry practices, I thought of doing a quick poll within this group:

Have you every reported inconclusive data at submission utilizing DT other than in the screening tier?

Have agencies ever requested reporting inconclusive data based on confirmatory and other characterization assays?

I'd appreciate both "No" and "Yes" responses. If "Yes," it would be helpful to know the general rationale behind the request.

Thank you for your feedback

Elisa

Hi Elisa,

                My answer to both your questions is No. In my experience, we never reported "inconclusive" ADA results in any of the tiers. To my knowledge we were never challenged by health authorities for not using "inconclusive" category in immunogenicity reporting. I am strongly against such "inconclusive" results, and I'd like to use this opportunity to climb my soapbox with my favorite arguments:

• ·         You could argue that any ADA-negative result should be reported as "inconclusive" since our assays have limited sensitivity and a more sensitive assay might be able to detect ADA in samples previously classified as negative.
• ·         We do occasionally detect ADA in the presence of drug concentrations that exceed drug tolerance. We don't report such results as "false positive" or "I can't believe it's positive", but as regular positives without any qualifiers. This is because both negative and positive result obtained in the presence of drug are quite conclusive, which brings me to my next point.
• ·         Picture an assay that cannot detect 100 ng/mL of ADA in the presence of 50 µg/mL of drug but can reliably detect 200 ng/mL ADA. A negative classification in the presence of 50 µg/mL means that ADA level in the sample is <200 ng/mL, which is quite conclusive. In this case, a negative result does provide valuable information and should not be discarded as "inconclusive".

Now, I'm going to climb down from my soapbox and decamp for the kitchens to inspect the contents for the fridge in preparation for tomorrow 😊.

Hi everyone,

I've been exploring this topic within my organization and wanted to gather broader insights. From my current understanding, and that of my bioanalytical colleagues, the drug tolerance from the screening assay is typically used to determine the presence of inconclusive samples. I have been recently on discussions whether drug tolerance from confirmatory assays, nAb, and other characterization tiers should be considered as well.

To better understand industry practices, I thought of doing a quick poll within this group:

Have you every reported inconclusive data at submission utilizing DT other than in the screening tier?

Have agencies ever requested reporting inconclusive data based on confirmatory and other characterization assays?

I'd appreciate both "No" and "Yes" responses. If "Yes," it would be helpful to know the general rationale behind the request.

Thank you for your feedback

Elisa

Hi Elisa,

                My answer to both your questions is No. In my experience, we never reported "inconclusive" ADA results in any of the tiers. To my knowledge we were never challenged by health authorities for not using "inconclusive" category in immunogenicity reporting. I am strongly against such "inconclusive" results, and I'd like to use this opportunity to climb my soapbox with my favorite arguments:

• ·         You could argue that any ADA-negative result should be reported as "inconclusive" since our assays have limited sensitivity and a more sensitive assay might be able to detect ADA in samples previously classified as negative.
• ·         We do occasionally detect ADA in the presence of drug concentrations that exceed drug tolerance. We don't report such results as "false positive" or "I can't believe it's positive", but as regular positives without any qualifiers. This is because both negative and positive result obtained in the presence of drug are quite conclusive, which brings me to my next point.
• ·         Picture an assay that cannot detect 100 ng/mL of ADA in the presence of 50 µg/mL of drug but can reliably detect 200 ng/mL ADA. A negative classification in the presence of 50 µg/mL means that ADA level in the sample is <200 ng/mL, which is quite conclusive. In this case, a negative result does provide valuable information and should not be discarded as "inconclusive".

Now, I'm going to climb down from my soapbox and decamp for the kitchens to inspect the contents for the fridge in preparation for tomorrow 😊.

Hi everyone,

I've been exploring this topic within my organization and wanted to gather broader insights. From my current understanding, and that of my bioanalytical colleagues, the drug tolerance from the screening assay is typically used to determine the presence of inconclusive samples. I have been recently on discussions whether drug tolerance from confirmatory assays, nAb, and other characterization tiers should be considered as well.

To better understand industry practices, I thought of doing a quick poll within this group:

Have you every reported inconclusive data at submission utilizing DT other than in the screening tier?

Have agencies ever requested reporting inconclusive data based on confirmatory and other characterization assays?

I'd appreciate both "No" and "Yes" responses. If "Yes," it would be helpful to know the general rationale behind the request.

Thank you for your feedback

Elisa

Hi Elisa,

                My answer to both your questions is No. In my experience, we never reported "inconclusive" ADA results in any of the tiers. To my knowledge we were never challenged by health authorities for not using "inconclusive" category in immunogenicity reporting. I am strongly against such "inconclusive" results, and I'd like to use this opportunity to climb my soapbox with my favorite arguments:

• ·         You could argue that any ADA-negative result should be reported as "inconclusive" since our assays have limited sensitivity and a more sensitive assay might be able to detect ADA in samples previously classified as negative.
• ·         We do occasionally detect ADA in the presence of drug concentrations that exceed drug tolerance. We don't report such results as "false positive" or "I can't believe it's positive", but as regular positives without any qualifiers. This is because both negative and positive result obtained in the presence of drug are quite conclusive, which brings me to my next point.
• ·         Picture an assay that cannot detect 100 ng/mL of ADA in the presence of 50 µg/mL of drug but can reliably detect 200 ng/mL ADA. A negative classification in the presence of 50 µg/mL means that ADA level in the sample is <200 ng/mL, which is quite conclusive. In this case, a negative result does provide valuable information and should not be discarded as "inconclusive".

Now, I'm going to climb down from my soapbox and decamp for the kitchens to inspect the contents for the fridge in preparation for tomorrow 😊.

Hi everyone,

I've been exploring this topic within my organization and wanted to gather broader insights. From my current understanding, and that of my bioanalytical colleagues, the drug tolerance from the screening assay is typically used to determine the presence of inconclusive samples. I have been recently on discussions whether drug tolerance from confirmatory assays, nAb, and other characterization tiers should be considered as well.

To better understand industry practices, I thought of doing a quick poll within this group:

Have you every reported inconclusive data at submission utilizing DT other than in the screening tier?

Have agencies ever requested reporting inconclusive data based on confirmatory and other characterization assays?

I'd appreciate both "No" and "Yes" responses. If "Yes," it would be helpful to know the general rationale behind the request.

Thank you for your feedback

Elisa

Hi everyone,

I've been exploring this topic within my organization and wanted to gather broader insights. From my current understanding, and that of my bioanalytical colleagues, the drug tolerance from the screening assay is typically used to determine the presence of inconclusive samples. I have been recently on discussions whether drug tolerance from confirmatory assays, nAb, and other characterization tiers should be considered as well.

To better understand industry practices, I thought of doing a quick poll within this group:

Have you every reported inconclusive data at submission utilizing DT other than in the screening tier?

Have agencies ever requested reporting inconclusive data based on confirmatory and other characterization assays?

I'd appreciate both "No" and "Yes" responses. If "Yes," it would be helpful to know the general rationale behind the request.

Thank you for your feedback

Elisa