Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Dear all,

I have a question related to the submission of IRB approvals in the case of an IND protocol amendment, as well as IRB-approved ICF (in addition to the ICF template from the sponsor) when there is an update in the ICF. 

I couldn't find any guidance or CFR section that mention such requirements but I always submit it as a precautionary measure. In terms of timing, I consider that these documents have to be sent in the 30 days following the implementation of the change once it is IRB approved.
However, this can be challenging when it is a multicenter study and we do not receive the IRB approvals and the IRB-approved ICF at the same time.

Could you provide any advise here? Do you always submit IRB approvals in the 30d window for protocol amendments, and all the IRB-approved ICF each time there is a change in the ICF? Or is it something you assess based on the change being critical or minor?

Thank you,

Best Regards

In my experience, I have never submitted IRB approvals to an IND. Obtaining IRB approvals is of course required for any change in a protocol or ICF, but submission of those approvals to the IND is not required. In addition, I have only submitted ICFs to the IND when specifically requested by the Agency. The only regulatory expectation for a 30-day window with respect to an IND is the 30-day review period for the original IND submission and for submission of new investigators on a monthly basis. Submission of protocol amendments to the IND do not have a 30-day wait to implement the amendment.

------------------------------
Glen Park PharmD
Vice President, Regulatory Affairs and Quality Assurance
New York NY
United States
------------------------------

Original Message:
Sent: 01-Apr-2021 13:19
From: Anonymous Member
Subject: IND Protocol amendments and IRB Approval/ ICF submission

This message was posted by a user wishing to remain anonymous

Dear all,

I have a question related to the submission of IRB approvals in the case of an IND protocol amendment, as well as IRB-approved ICF (in addition to the ICF template from the sponsor) when there is an update in the ICF.

I couldn't find any guidance or CFR section that mention such requirements but I always submit it as a precautionary measure. In terms of timing, I consider that these documents have to be sent in the 30 days following the implementation of the change once it is IRB approved.
However, this can be challenging when it is a multicenter study and we do not receive the IRB approvals and the IRB-approved ICF at the same time.

Could you provide any advise here? Do you always submit IRB approvals in the 30d window for protocol amendments, and all the IRB-approved ICF each time there is a change in the ICF? Or is it something you assess based on the change being critical or minor?

Thank you,

Best Regards

This message was posted by a user wishing to remain anonymous

If you were looking to add a phase III stage to your phase II study protocol, would you need FDA to comment/approve your Protocol Amendment or can you implement after IRB approval? Would a more conservative approach be to contact FDA to confirm that they are in agreement with the proposed changes or how should this be handled?
Original Message:
Sent: 02-Apr-2021 08:29
From: Glen Park
Subject: IND Protocol amendments and IRB Approval/ ICF submission

In my experience, I have never submitted IRB approvals to an IND. Obtaining IRB approvals is of course required for any change in a protocol or ICF, but submission of those approvals to the IND is not required. In addition, I have only submitted ICFs to the IND when specifically requested by the Agency. The only regulatory expectation for a 30-day window with respect to an IND is the 30-day review period for the original IND submission and for submission of new investigators on a monthly basis. Submission of protocol amendments to the IND do not have a 30-day wait to implement the amendment.

------------------------------
Glen Park PharmD
Vice President, Regulatory Affairs and Quality Assurance
New York NY
United States

Original Message:
Sent: 01-Apr-2021 13:19
From: Anonymous Member
Subject: IND Protocol amendments and IRB Approval/ ICF submission

This message was posted by a user wishing to remain anonymous

Dear all,

I have a question related to the submission of IRB approvals in the case of an IND protocol amendment, as well as IRB-approved ICF (in addition to the ICF template from the sponsor) when there is an update in the ICF.

I couldn't find any guidance or CFR section that mention such requirements but I always submit it as a precautionary measure. In terms of timing, I consider that these documents have to be sent in the 30 days following the implementation of the change once it is IRB approved.
However, this can be challenging when it is a multicenter study and we do not receive the IRB approvals and the IRB-approved ICF at the same time.

Could you provide any advise here? Do you always submit IRB approvals in the 30d window for protocol amendments, and all the IRB-approved ICF each time there is a change in the ICF? Or is it something you assess based on the change being critical or minor?

Thank you,

Best Regards

You can submit the phase III stage to your phase II even without the IRB approval. As far as waiting for FDA to comment on your phase III stage amendment, they may not comment at all unless this phase III stage of protocol has any safety implications, then they would reach out to you promptly! Basically you don't need to wait but if this phase III stage is pivotal and you are hoping to convert this study to a registration trial then Id recommend (you don't need to but the risk is at the time of NDA/BLA the FDA may not accept this trial as pivotal citing various reasons like  choice of endpoint or population chosen for the proposed indication not acceptable etc then a big delay since you may have to repeat the trial.... ) you submit this part as a Special Protocol Assessment (SPA) for which there is a 45 days review. Just so you are aware, to date CDER has not had formal expectations for the extent and timeliness of review of most of these type of drug development submissions.

------------------------------
GRSAOnline
------------------------------

Original Message:
Sent: 04-May-2021 14:20
From: Anonymous Member
Subject: IND Protocol amendments and IRB Approval/ ICF submission

This message was posted by a user wishing to remain anonymous

If you were looking to add a phase III stage to your phase II study protocol, would you need FDA to comment/approve your Protocol Amendment or can you implement after IRB approval? Would a more conservative approach be to contact FDA to confirm that they are in agreement with the proposed changes or how should this be handled?
Original Message:
Sent: 02-Apr-2021 08:29
From: Glen Park
Subject: IND Protocol amendments and IRB Approval/ ICF submission

In my experience, I have never submitted IRB approvals to an IND. Obtaining IRB approvals is of course required for any change in a protocol or ICF, but submission of those approvals to the IND is not required. In addition, I have only submitted ICFs to the IND when specifically requested by the Agency. The only regulatory expectation for a 30-day window with respect to an IND is the 30-day review period for the original IND submission and for submission of new investigators on a monthly basis. Submission of protocol amendments to the IND do not have a 30-day wait to implement the amendment.

------------------------------
Glen Park PharmD
Vice President, Regulatory Affairs and Quality Assurance
New York NY
United States

Original Message:
Sent: 01-Apr-2021 13:19
From: Anonymous Member
Subject: IND Protocol amendments and IRB Approval/ ICF submission

This message was posted by a user wishing to remain anonymous

Dear all,

I have a question related to the submission of IRB approvals in the case of an IND protocol amendment, as well as IRB-approved ICF (in addition to the ICF template from the sponsor) when there is an update in the ICF.

I couldn't find any guidance or CFR section that mention such requirements but I always submit it as a precautionary measure. In terms of timing, I consider that these documents have to be sent in the 30 days following the implementation of the change once it is IRB approved.
However, this can be challenging when it is a multicenter study and we do not receive the IRB approvals and the IRB-approved ICF at the same time.

Could you provide any advise here? Do you always submit IRB approvals in the 30d window for protocol amendments, and all the IRB-approved ICF each time there is a change in the ICF? Or is it something you assess based on the change being critical or minor?

Thank you,

Best Regards

This message was posted by a user wishing to remain anonymous

are you talking about submitting a protocol amendment to the FDA/IND? You don't need to wait for IRB approvals to submit a protocol amendment to the FDA/IND.
Original Message:
Sent: 01-Apr-2021 13:19
From: Anonymous Member
Subject: IND Protocol amendments and IRB Approval/ ICF submission

This message was posted by a user wishing to remain anonymous

Dear all,

I have a question related to the submission of IRB approvals in the case of an IND protocol amendment, as well as IRB-approved ICF (in addition to the ICF template from the sponsor) when there is an update in the ICF.

I couldn't find any guidance or CFR section that mention such requirements but I always submit it as a precautionary measure. In terms of timing, I consider that these documents have to be sent in the 30 days following the implementation of the change once it is IRB approved.
However, this can be challenging when it is a multicenter study and we do not receive the IRB approvals and the IRB-approved ICF at the same time.

Could you provide any advise here? Do you always submit IRB approvals in the 30d window for protocol amendments, and all the IRB-approved ICF each time there is a change in the ICF? Or is it something you assess based on the change being critical or minor?

Thank you,

Best Regards

It is not necessary to submit IRB approval letters and modified ICFs to the IND.  Typically it is only necessary to submit the revised protocol.  You should have an internal process to track all IRB approvals and to assure that it is received before implementing a change at a site, but you don't need to submit the IRB approvals to FDA.

------------------------------
Michael Hamrell, Ph.D., RAC, FRAPS
Huntington Beach CA
United States
------------------------------

Original Message:
Sent: 01-Apr-2021 13:19
From: Anonymous Member
Subject: IND Protocol amendments and IRB Approval/ ICF submission

This message was posted by a user wishing to remain anonymous

Dear all,

I have a question related to the submission of IRB approvals in the case of an IND protocol amendment, as well as IRB-approved ICF (in addition to the ICF template from the sponsor) when there is an update in the ICF.

I couldn't find any guidance or CFR section that mention such requirements but I always submit it as a precautionary measure. In terms of timing, I consider that these documents have to be sent in the 30 days following the implementation of the change once it is IRB approved.
However, this can be challenging when it is a multicenter study and we do not receive the IRB approvals and the IRB-approved ICF at the same time.

Could you provide any advise here? Do you always submit IRB approvals in the 30d window for protocol amendments, and all the IRB-approved ICF each time there is a change in the ICF? Or is it something you assess based on the change being critical or minor?

Thank you,

Best Regards