Regulatory Open Forum

We have multiple open INDs for this investigational product in development. The CMC info has been submitted to the parent IND. A new manufacturing process is being introduced, material from which will be introduced in new initiated clinical trials only (not ongoing trials). In such a case, is it acceptable/advisable to submit the CMC info on the new manufacturing process to the parent IND and clarify in the cover letter that this material will be applied to new initiated trials only OR is it better to submit this info to the IND of the newly initiated trial? What would be the pros and cons in either case.
thank you in advance.

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Saloni Vora
Quincy MA
United States
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This message was posted by a user wishing to remain anonymous

Normally, you'd submit the CMC amendment with the protocol or protocol amendment that plans to use the new material. I'd recommend your second option!
Original Message:
Sent: 03-Mar-2021 09:21
From: Saloni Vora
Subject: Approach on submission of CMC information to the IND

We have multiple open INDs for this investigational product in development. The CMC info has been submitted to the parent IND. A new manufacturing process is being introduced, material from which will be introduced in new initiated clinical trials only (not ongoing trials). In such a case, is it acceptable/advisable to submit the CMC info on the new manufacturing process to the parent IND and clarify in the cover letter that this material will be applied to new initiated trials only OR is it better to submit this info to the IND of the newly initiated trial? What would be the pros and cons in either case.
thank you in advance.

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Saloni Vora
Quincy MA
United States
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Hi Saloni,

We do this frequently in oncology trials in having a parent IND in one oncology division then child INDs in other oncology divisions.  So long as the CMC changes affect the investigational product used in all the clinical studies, I would submit the new CMC information to the parent IND then, in the cover letter for the protocol/amendment to the child IND, include a cross reference to the updated CMC information in the parent IND.

More complexity is involved if the new CMC information is only relevant to the protocol/amendment in the child IND.  In this case, the new CMC information should definitely be submitted to the child IND with the protocol/amendment.

Feel free to reach out to me directly through LinkedIn if you need/want more specific feedback.

Good luck!

Mark

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Mark De Rosch, PhD, FRAPS
Epizyme, Inc.
Cambridge, MA
United States
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Original Message:
Sent: 03-Mar-2021 09:53
From: Anonymous Member
Subject: Approach on submission of CMC information to the IND

This message was posted by a user wishing to remain anonymous

Normally, you'd submit the CMC amendment with the protocol or protocol amendment that plans to use the new material. I'd recommend your second option!
Original Message:
Sent: 03-Mar-2021 09:21
From: Saloni Vora
Subject: Approach on submission of CMC information to the IND

We have multiple open INDs for this investigational product in development. The CMC info has been submitted to the parent IND. A new manufacturing process is being introduced, material from which will be introduced in new initiated clinical trials only (not ongoing trials). In such a case, is it acceptable/advisable to submit the CMC info on the new manufacturing process to the parent IND and clarify in the cover letter that this material will be applied to new initiated trials only OR is it better to submit this info to the IND of the newly initiated trial? What would be the pros and cons in either case.
thank you in advance.

------------------------------
Saloni Vora
Quincy MA
United States
------------------------------

You could also email your FDA PM.  I assume all of your INDs are in the same division, but if not you may want to email your PMs in each division. I'm handling a similar situation (two INDs in same division). While we only have one process, each program utilizes a different container closure (one uses blisters and one uses bottles), but I am still filing all CMC to the parent IND. I think if you start filing different CMC information to different INDs, you may risk confusing CMC reviewers or they may miss something because it's in a different IND.  As long as you are clear and organized in the parent IND it may be better for reviewers. Again, I suggest running this by your PMs.

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Tom
Senior Director, Regulatory Affairs CMC
Chicago
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Original Message:
Sent: 03-Mar-2021 09:21
From: Saloni Vora
Subject: Approach on submission of CMC information to the IND

We have multiple open INDs for this investigational product in development. The CMC info has been submitted to the parent IND. A new manufacturing process is being introduced, material from which will be introduced in new initiated clinical trials only (not ongoing trials). In such a case, is it acceptable/advisable to submit the CMC info on the new manufacturing process to the parent IND and clarify in the cover letter that this material will be applied to new initiated trials only OR is it better to submit this info to the IND of the newly initiated trial? What would be the pros and cons in either case.
thank you in advance.

------------------------------
Saloni Vora
Quincy MA
United States
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As a former FDA CMC reviewer I would agree to keep CMC information cross-referenced.

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Mamta Gautam-Basak
Senior Director, RA CMC
North Potomac MD
United States
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Original Message:
Sent: 04-Mar-2021 13:07
From: Tom Stothoff
Subject: Approach on submission of CMC information to the IND

You could also email your FDA PM.  I assume all of your INDs are in the same division, but if not you may want to email your PMs in each division. I'm handling a similar situation (two INDs in same division). While we only have one process, each program utilizes a different container closure (one uses blisters and one uses bottles), but I am still filing all CMC to the parent IND. I think if you start filing different CMC information to different INDs, you may risk confusing CMC reviewers or they may miss something because it's in a different IND.  As long as you are clear and organized in the parent IND it may be better for reviewers. Again, I suggest running this by your PMs.

------------------------------
Tom
Senior Director, Regulatory Affairs CMC
Chicago

Original Message:
Sent: 03-Mar-2021 09:21
From: Saloni Vora
Subject: Approach on submission of CMC information to the IND

We have multiple open INDs for this investigational product in development. The CMC info has been submitted to the parent IND. A new manufacturing process is being introduced, material from which will be introduced in new initiated clinical trials only (not ongoing trials). In such a case, is it acceptable/advisable to submit the CMC info on the new manufacturing process to the parent IND and clarify in the cover letter that this material will be applied to new initiated trials only OR is it better to submit this info to the IND of the newly initiated trial? What would be the pros and cons in either case.
thank you in advance.

------------------------------
Saloni Vora
Quincy MA
United States
------------------------------

This message was posted by a user wishing to remain anonymous

Anon,
Your question is related specifically to new process being introduced for the clinical material (i.e. not packaging related) and therefore its a reviewable amendment from the FDA perspective from a safety stand point on the patients who will be dosed with this modified material, which consequently has an immediate impact on the study protocol which plans to use it! In this particular situation, I'd strongly file it to the IND which is planning to use this modified process material. The rest of the INDs which have no impact could just cc'd the cover letter. 
Hope this helps!
Original Message:
Sent: 03-Mar-2021 09:21
From: Saloni Vora
Subject: Approach on submission of CMC information to the IND

We have multiple open INDs for this investigational product in development. The CMC info has been submitted to the parent IND. A new manufacturing process is being introduced, material from which will be introduced in new initiated clinical trials only (not ongoing trials). In such a case, is it acceptable/advisable to submit the CMC info on the new manufacturing process to the parent IND and clarify in the cover letter that this material will be applied to new initiated trials only OR is it better to submit this info to the IND of the newly initiated trial? What would be the pros and cons in either case.
thank you in advance.

------------------------------
Saloni Vora
Quincy MA
United States
------------------------------

I have to disagree with this last post.

We do this - file all CMC information to the first IND that was submitted, regardless of which study it is being used in. This has included opening a new IND for a new indication and just cross-referencing the first IND for the CMC information. In the cover letter we reference both IND numbers - the one where the CMC information resides and the one governing the study where that particular material will be used. We've never had any pushback from FDA on this approach, and I think it really has the least possibility of confusion and error, particularly when it comes to lifecycle management.

The one case I can see where there might be advantage to not doing it this way is if you have a particular CMC aspect (e.g., formulation, primary packaging) that really is specific to one indication that would never be used for the others. In our case, the same material is ultimately intended for all indications, but we're in different stages of CMC development when each study starts.

You do have to be careful that you add the updated information as new and not replace if the original information is still applicable to ongoing trials.

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Rachel Thornton
Associate Director
Smyrna GA
United States
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Original Message:
Sent: 04-Mar-2021 17:04
From: Anonymous Member
Subject: Approach on submission of CMC information to the IND

This message was posted by a user wishing to remain anonymous

Anon,
Your question is related specifically to new process being introduced for the clinical material (i.e. not packaging related) and therefore its a reviewable amendment from the FDA perspective from a safety stand point on the patients who will be dosed with this modified material, which consequently has an immediate impact on the study protocol which plans to use it! In this particular situation, I'd strongly file it to the IND which is planning to use this modified process material. The rest of the INDs which have no impact could just cc'd the cover letter.
Hope this helps!
Original Message:
Sent: 03-Mar-2021 09:21
From: Saloni Vora
Subject: Approach on submission of CMC information to the IND

We have multiple open INDs for this investigational product in development. The CMC info has been submitted to the parent IND. A new manufacturing process is being introduced, material from which will be introduced in new initiated clinical trials only (not ongoing trials). In such a case, is it acceptable/advisable to submit the CMC info on the new manufacturing process to the parent IND and clarify in the cover letter that this material will be applied to new initiated trials only OR is it better to submit this info to the IND of the newly initiated trial? What would be the pros and cons in either case.
thank you in advance.

------------------------------
Saloni Vora
Quincy MA
United States
------------------------------

This message was posted by a user wishing to remain anonymous

"The one case I can see where there might be advantage to not doing it this way is if you have a particular CMC aspect (e.g., formulation, primary packaging) that really is specific to one indication that would never be used for the others. In our case, the same material is ultimately intended for all indications, but we're in different stages of CMC development when each study starts."

This is why I'd file it with the IND that is impacted immediately and cross reference to other INDs since details are not provided by the original question. There is no agreement or disagreement, one can do either way! As the former FDA reviewer said, the rest of the INDs which have no impact could just be cross referenced!
Original Message:
Sent: 08-Mar-2021 09:59
From: Rachel Thornton
Subject: Approach on submission of CMC information to the IND

I have to disagree with this last post.

We do this - file all CMC information to the first IND that was submitted, regardless of which study it is being used in. This has included opening a new IND for a new indication and just cross-referencing the first IND for the CMC information. In the cover letter we reference both IND numbers - the one where the CMC information resides and the one governing the study where that particular material will be used. We've never had any pushback from FDA on this approach, and I think it really has the least possibility of confusion and error, particularly when it comes to lifecycle management.

The one case I can see where there might be advantage to not doing it this way is if you have a particular CMC aspect (e.g., formulation, primary packaging) that really is specific to one indication that would never be used for the others. In our case, the same material is ultimately intended for all indications, but we're in different stages of CMC development when each study starts.

You do have to be careful that you add the updated information as new and not replace if the original information is still applicable to ongoing trials.

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

Original Message:
Sent: 04-Mar-2021 17:04
From: Anonymous Member
Subject: Approach on submission of CMC information to the IND

This message was posted by a user wishing to remain anonymous

Anon,
Your question is related specifically to new process being introduced for the clinical material (i.e. not packaging related) and therefore its a reviewable amendment from the FDA perspective from a safety stand point on the patients who will be dosed with this modified material, which consequently has an immediate impact on the study protocol which plans to use it! In this particular situation, I'd strongly file it to the IND which is planning to use this modified process material. The rest of the INDs which have no impact could just cc'd the cover letter.
Hope this helps!
Original Message:
Sent: 03-Mar-2021 09:21
From: Saloni Vora
Subject: Approach on submission of CMC information to the IND

We have multiple open INDs for this investigational product in development. The CMC info has been submitted to the parent IND. A new manufacturing process is being introduced, material from which will be introduced in new initiated clinical trials only (not ongoing trials). In such a case, is it acceptable/advisable to submit the CMC info on the new manufacturing process to the parent IND and clarify in the cover letter that this material will be applied to new initiated trials only OR is it better to submit this info to the IND of the newly initiated trial? What would be the pros and cons in either case.
thank you in advance.

------------------------------
Saloni Vora
Quincy MA
United States
------------------------------