Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hello All,

We have a clinical trial where we have a comparator drug, but the comparator is commercial in the EU. For some reason it got held up in customs since it is considered a foreign drug. However, our IND was initially approved by the FDA. Now they are asking why we are using a foreign comparator drug and to justify the use. Has anyone had experience with this? Also, I'm not sure why we cannot have a foreign comparator drug on the clinical trial. Does the comparator arm in the clinical trial have to be commercial in the US?

This message was posted by a user wishing to remain anonymous

I'm curious about this as well as the opposite scenario, importing a US licensed product to EU. What if the comparator is changed due to blinding and imported as a clinical study material? 

Original Message:
Sent: 17-Jan-2023 17:06
From: Anonymous Member
Subject: Foreign Comparator Drug

This message was posted by a user wishing to remain anonymous

Hello All,

We have a clinical trial where we have a comparator drug, but the comparator is commercial in the EU. For some reason it got held up in customs since it is considered a foreign drug. However, our IND was initially approved by the FDA. Now they are asking why we are using a foreign comparator drug and to justify the use. Has anyone had experience with this? Also, I'm not sure why we cannot have a foreign comparator drug on the clinical trial. Does the comparator arm in the clinical trial have to be commercial in the US?

I don't understand how you could use a drug in a study as a comparator without it being approved or generic in the country of the trail or under an IND in the US. And a drug under an another IND or off label use of a drug should not be an active comparator for a drug seeking approval (since these drugs are not approved by the fda). I would think your EU participants would be compared to the comparator but other countries would not have that arm of the trial…. Of course the data of the h2h could be shared with other countries (and should) it would be as fyi and not be critical for approval since the drug isn't approved in those countries. Interested to hear what happens on your trial, if you would please follow up. 

------------------------------
Stephanie Markey
Associate Director
Fraser CO
United States
------------------------------

Original Message:
Sent: 17-Jan-2023 17:06
From: Anonymous Member
Subject: Foreign Comparator Drug

This message was posted by a user wishing to remain anonymous

Hello All,

We have a clinical trial where we have a comparator drug, but the comparator is commercial in the EU. For some reason it got held up in customs since it is considered a foreign drug. However, our IND was initially approved by the FDA. Now they are asking why we are using a foreign comparator drug and to justify the use. Has anyone had experience with this? Also, I'm not sure why we cannot have a foreign comparator drug on the clinical trial. Does the comparator arm in the clinical trial have to be commercial in the US?

This message was posted by a user wishing to remain anonymous

This is an interesting point.

I do remember previously working for a large company that was very cautious about the comparator strategy because at the end of the day it could impact the claim that was made and the understanding of "improvement" versus available medication. If the drug you are using is not on the market in the country then what is your claim?

Original Message:
Sent: 17-Jan-2023 17:06
From: Anonymous Member
Subject: Foreign Comparator Drug

This message was posted by a user wishing to remain anonymous

Hello All,

We have a clinical trial where we have a comparator drug, but the comparator is commercial in the EU. For some reason it got held up in customs since it is considered a foreign drug. However, our IND was initially approved by the FDA. Now they are asking why we are using a foreign comparator drug and to justify the use. Has anyone had experience with this? Also, I'm not sure why we cannot have a foreign comparator drug on the clinical trial. Does the comparator arm in the clinical trial have to be commercial in the US?

I have a lot of experience with this, as I work for a European company, and our Clinical Supply function is always pushing to use EU-sourced comparator drug since it's generally less expensive.

First of all, no matter what comparator you're using, you have to report in your IND that you are using it. If it's a commercial product, you still need to say you're using it and describe any changes you might be making to it (e.g., for blinding purposes). So you should have submitted a 3.2.P section on it to your IND to begin with. 

Second, if the comparator you're using is approved in the EU but not in the US, then FDA considers it investigational and you would need full CMC information on it. Even if the drug is approved in the US, if you are using supplies sourced in the EU, such that it is not labeled with the NDC, FDA considers it investigational and you would need to provide full CMC information on it. Seems strange I know, but FDA has no way of knowing whether the EU-sourced material is equivalent to what they approved for the US. At least that's their position. This is all based on direct feedback we received from FDA. (note, this feedback is for mAb products; they could be less picky about small molecules, or it just might be easier to generate some comparability data to provide so they'll accept it).

So far, we've always used EU-sourced material in the EU & US-sourced material in the US, as we've never actually tried to make a superiority claim on the label in the US. Note that FDA has told us repeatedly that we would not be able to use clinical data generated against a non-US-sourced comparator to support label claims without providing comparability data between EU-sourced & US-sourced material.

------------------------------
Rachel Thornton
Director
Smyrna GA
United States
------------------------------

Original Message:
Sent: 17-Jan-2023 17:06
From: Anonymous Member
Subject: Foreign Comparator Drug

This message was posted by a user wishing to remain anonymous

Hello All,

We have a clinical trial where we have a comparator drug, but the comparator is commercial in the EU. For some reason it got held up in customs since it is considered a foreign drug. However, our IND was initially approved by the FDA. Now they are asking why we are using a foreign comparator drug and to justify the use. Has anyone had experience with this? Also, I'm not sure why we cannot have a foreign comparator drug on the clinical trial. Does the comparator arm in the clinical trial have to be commercial in the US?