Regulatory Open Forum

Dear Colleagues,

1. Does the use an approved drug product with an investigational drug product in a clinical trial render the approved drug product as an investigational drug product?  

2. Does the approved product have to be labeled as an investigational drug?

3. What if the drug product is approved in multiple countries but not for all of the same indications as the US label? 

4. Must US approved drug product be used in an EU clinical trial or can locally sourced approved drug product used?

Thank you for your assistance.

David Lucking

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David Lucking
FL
United States
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​Hi, David - a few answers from the US perspective (it sounds like this is for a US study? or at least to support a US marketing application?)...

1. Does the use an approved drug product with an investigational drug product in a clinical trial render the approved drug product as an investigational drug product?  

In the US, if the approved drug is used in accordance with its approved labeling, it is not considered an investigational product.  Information on the approved drug will still need to be included (in brief) in the IND.

2. Does the approved product have to be labeled as an investigational drug?

Not in the US, if used according to the label.  However, blinding issues may be a factor.

3. What if the drug product is approved in multiple countries but not for all of the same indications as the US label?

The CTAs filed in the other countries will need to reflect those regulations.   

4. Must US approved drug product be used in an EU clinical trial or can locally sourced approved drug product used?

If the EU clinical study is being used to support a US marketing application, locally sourced drug product may still be used. Information on that drug product (and any differences to the US drug product) will be required in the eventual US filing.


Hope this helps!

Cathy

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Catherine Anderson PhD, RAC
Associate Director - Regulatory CMC
Hillsborough NC
United States
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Original Message:
Sent: 19-Aug-2019 15:08
From: David Lucking
Subject: Use of Approved Drug Product with an Investigational Drug Product

Dear Colleagues,

1. Does the use an approved drug product with an investigational drug product in a clinical trial render the approved drug product as an investigational drug product?

2. Does the approved product have to be labeled as an investigational drug?

3. What if the drug product is approved in multiple countries but not for all of the same indications as the US label?

4. Must US approved drug product be used in an EU clinical trial or can locally sourced approved drug product used?

Thank you for your assistance.

David Lucking

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David Lucking
FL
United States
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Hi David,

My thoughts.

1. No, as long as the approved drug is used according to labeling in the study region. In global trials this can be tricky, but manageable. If it is a double-blind trial and there is modification of the approved drug by over-encapsulation, for example, that procedure and the associated data, such as stability, needs to be included in the IND/IMPD.
2. No, unless as noted in response to 1. there is some modification of the approved drug. 
3. Each country in which the study is conducted has to be conducted according to the labeling in that country. If the indication is not labeled, the drug product becomes investigational in that country. For ex-US that requires attention to how the CTA is presented. EMA has some guidances on how to deal with approved drugs that are not being used in their original form and for an un-approved indication.
4. A locally sourced drug product is generally acceptable, but you do have to be careful about who the manufacturer is. In the end there has to be no unresolvable question about the similarity between the products used in different countries.


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Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
Jersey City NJ
United States
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Original Message:
Sent: 19-Aug-2019 15:08
From: David Lucking
Subject: Use of Approved Drug Product with an Investigational Drug Product

Dear Colleagues,

1. Does the use an approved drug product with an investigational drug product in a clinical trial render the approved drug product as an investigational drug product?

2. Does the approved product have to be labeled as an investigational drug?

3. What if the drug product is approved in multiple countries but not for all of the same indications as the US label?

4. Must US approved drug product be used in an EU clinical trial or can locally sourced approved drug product used?

Thank you for your assistance.

David Lucking

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David Lucking
FL
United States
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