Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

Hello,

It is best to provide the Agency with the courtesy 30 day review. If they have questions after the 30 days, they will certainly reach out anytime. 

Best
Katrina

------------------------------
Katrina Chan
Sr Manager, Global Regulatory Affairs
Oakland CA
United States
------------------------------

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

I would definitely wait 30 d after transferring the IND because you will be naming a new manufacturer and will be submitting a protocol amendment.  I might suggest transferring the IND as Step 1, then submitting the new manufacturer (as a CMC amendment) and protocol (as a clinical amendment; both can be submitted together) as Step 2.  Once the IND is transferred, meaning that the old sponsor has informed FDA of the transfer and the new sponsor has informed FDA of accepting the transfer, you could submit the CMC & clinical amendments right away.  Then, wait 30 d for any comments from FDA.

Good luck!

------------------------------
Mark A. De Rosch, PhD, FRAPS
Chief Operating Officer
Aura Biosciences
Cambridge, MA
United States
------------------------------

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

There is nothing magical about waiting 30 days to see if FDA has any feedback. FDA does not have a regulation-defined clock for IND amendments (except related to clinical holds). If the old and new sponsors are both in communication with the PM, the review division will be well aware of the changes taking place and will advise the sponsor accordingly.

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

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

Yes agree with Glen.

------------------------------
Mamta Gautam-Basak
Senior Director, RA CMC
North Potomac MD
United States
------------------------------

Original Message:
Sent: 18-Mar-2021 08:42
From: Glen Park
Subject: CMC informational amendment to IND

There is nothing magical about waiting 30 days to see if FDA has any feedback. FDA does not have a regulation-defined clock for IND amendments (except related to clinical holds). If the old and new sponsors are both in communication with the PM, the review division will be well aware of the changes taking place and will advise the sponsor accordingly.

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

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

This message was posted by a user wishing to remain anonymous

This is helpful. Thank you very much. Once the IND is transferred, I'll have the amendment submitted. It's been some time since the previous sponsor has had activity so will need to open that pathway again (no new update letters were submitted annually so IND still assumed to be open). It's in the same division and expansion of a previously intended indication so will double check on IND status, etc. We will request a Type C meeting and can pose the question shortly after the submission within the BD as a quick check on the Quality front. Thank you.
Original Message:
Sent: 18-Mar-2021 08:42
From: Glen Park
Subject: CMC informational amendment to IND

There is nothing magical about waiting 30 days to see if FDA has any feedback. FDA does not have a regulation-defined clock for IND amendments (except related to clinical holds). If the old and new sponsors are both in communication with the PM, the review division will be well aware of the changes taking place and will advise the sponsor accordingly.

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

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

This message was posted by a user wishing to remain anonymous

No need to wait 30 days for an amendment to an already effective IND. FDA can come back with comments even after 30 days so this 30-day wait period is a moot point for an amendment.
Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

I agree with those who say no need to wait 30dys for the CMC amendment. 

I can see waiting 30dys (or until you hear back) re. the protocol amendment for the new trial, but they don't have to be submitted at the same time and you are unlikely to get questions on the CMC part if it's only a change in manufacturing site (unless you have a history of GMP problems). And, as others said, there's nothing that precludes the Agency from asking for information even after the 30dys. And if you've discussed everything with the Agency beforehand, I really see not purpose in waiting, at least for the CMC part. Clinical considerations are outside my experience, so I can't really advise on that part.

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

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

So.... has something changed here?  What phase of trials is this in with change of manufacturer?  Maybe you don't HAVE to wait 30 days on CMC but I have really never seen no process changes when something is transferred to a new drug manufacturing facility.    

Dependent on what process is moved to a new facility,  (packaging of tablet for example versus full drug product manufacturing or API ).  Know your risks.

And on a side note... becomes more risk as you move into Phase 3 pivotals.


------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com
------------------------------

Original Message:
Sent: 22-Mar-2021 12:52
From: Rachel Thornton
Subject: CMC informational amendment to IND

I agree with those who say no need to wait 30dys for the CMC amendment.

I can see waiting 30dys (or until you hear back) re. the protocol amendment for the new trial, but they don't have to be submitted at the same time and you are unlikely to get questions on the CMC part if it's only a change in manufacturing site (unless you have a history of GMP problems). And, as others said, there's nothing that precludes the Agency from asking for information even after the 30dys. And if you've discussed everything with the Agency beforehand, I really see not purpose in waiting, at least for the CMC part. Clinical considerations are outside my experience, so I can't really advise on that part.

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

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

I'll just say that in my 19 years in Reg CMC (vaccines and biologicals), CMC hardly ever gets questions on an IND amendment, and even when we do, they do not result in clinical hold. Even for Ph3 pivotal trials. The fact is, the focus is on the clinical side. At the companies I've worked for, we've always taken a "no waiting" approach. IMO, it is very low risk to not wait. But, of course, if you can afford the time, then it doesn't hurt to wait.

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

Original Message:
Sent: 23-Mar-2021 08:24
From: Ginger Cantor
Subject: CMC informational amendment to IND

So.... has something changed here?  What phase of trials is this in with change of manufacturer?  Maybe you don't HAVE to wait 30 days on CMC but I have really never seen no process changes when something is transferred to a new drug manufacturing facility.

Dependent on what process is moved to a new facility,  (packaging of tablet for example versus full drug product manufacturing or API ).  Know your risks.

And on a side note... becomes more risk as you move into Phase 3 pivotals.


------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com

Original Message:
Sent: 22-Mar-2021 12:52
From: Rachel Thornton
Subject: CMC informational amendment to IND

I agree with those who say no need to wait 30dys for the CMC amendment.

I can see waiting 30dys (or until you hear back) re. the protocol amendment for the new trial, but they don't have to be submitted at the same time and you are unlikely to get questions on the CMC part if it's only a change in manufacturing site (unless you have a history of GMP problems). And, as others said, there's nothing that precludes the Agency from asking for information even after the 30dys. And if you've discussed everything with the Agency beforehand, I really see not purpose in waiting, at least for the CMC part. Clinical considerations are outside my experience, so I can't really advise on that part.

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

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

Hi Rachel

Oh,  I worked in CMC in biologicals and pharma for 7 years.    Definitely had FDA questions  transferring plants,  most especially in Phase 3, where I lead a very large CMC meeting at FDA,  separate from  EOP2 to discuss plans  for joint API mfg then ultimately final drug manufacture being was transferred to a partner during Phase 3 CTM supply and resupply and post-market.  And the  Agency did ask about process equivalency, method transfer, validtion, etc.

At a small biopharma company (early 90s) I was QA Manager and did a lot  of supplier qualification audits. I audited a facility for GMPs to make Phase 1 supplies and strongly recommended against them as a supplier.  Just not hygienic, poor controls, etc.  My VP, a know nothing MD PhD overruled me to meet an investor timeline because the facility was lower cost, closer, and  "only going to be used for Phase 1".  Product was to go into AIDS patients.   He submitted the IND to CBER listing that facility as manufacturer of the CTM.  FDA Director called him up (way before 30 days)  and said "you will not use that facility, absolutely not, we will put you on clinical hold". Amazingly he told me I was right. Killed him to do it though.

So, I have seen it happen. If you have the time to wait, why not? Artificial deadlines set by management to please investors who don't care about anything but profits, usually. 




------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com
------------------------------

Original Message:
Sent: 23-Mar-2021 09:00
From: Rachel Thornton
Subject: CMC informational amendment to IND

I'll just say that in my 19 years in Reg CMC (vaccines and biologicals), CMC hardly ever gets questions on an IND amendment, and even when we do, they do not result in clinical hold. Even for Ph3 pivotal trials. The fact is, the focus is on the clinical side. At the companies I've worked for, we've always taken a "no waiting" approach. IMO, it is very low risk to not wait. But, of course, if you can afford the time, then it doesn't hurt to wait.

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

Original Message:
Sent: 23-Mar-2021 08:24
From: Ginger Cantor
Subject: CMC informational amendment to IND

So.... has something changed here?  What phase of trials is this in with change of manufacturer?  Maybe you don't HAVE to wait 30 days on CMC but I have really never seen no process changes when something is transferred to a new drug manufacturing facility.

Dependent on what process is moved to a new facility,  (packaging of tablet for example versus full drug product manufacturing or API ).  Know your risks.

And on a side note... becomes more risk as you move into Phase 3 pivotals.


------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com

Original Message:
Sent: 22-Mar-2021 12:52
From: Rachel Thornton
Subject: CMC informational amendment to IND

I agree with those who say no need to wait 30dys for the CMC amendment.

I can see waiting 30dys (or until you hear back) re. the protocol amendment for the new trial, but they don't have to be submitted at the same time and you are unlikely to get questions on the CMC part if it's only a change in manufacturing site (unless you have a history of GMP problems). And, as others said, there's nothing that precludes the Agency from asking for information even after the 30dys. And if you've discussed everything with the Agency beforehand, I really see not purpose in waiting, at least for the CMC part. Clinical considerations are outside my experience, so I can't really advise on that part.

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

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!

Then I guess the answer is, as it so often seems to be in RA, "it depends". It depends on the specifics of your product, the complexity of what you're doing, and whether you're transferring to a dodgy facility.

If there's something that raises a red flag to you as an RA professional - the site has a questionable GMP history, you're doing something unconventional, you have data to indicate things may not be as straightforward as one might have expected - then by all means, wait.

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

Original Message:
Sent: 23-Mar-2021 09:31
From: Ginger Cantor
Subject: CMC informational amendment to IND

Hi Rachel

Oh,  I worked in CMC in biologicals and pharma for 7 years.    Definitely had FDA questions  transferring plants,  most especially in Phase 3, where I lead a very large CMC meeting at FDA,  separate from  EOP2 to discuss plans  for joint API mfg then ultimately final drug manufacture being was transferred to a partner during Phase 3 CTM supply and resupply and post-market.  And the  Agency did ask about process equivalency, method transfer, validtion, etc.

At a small biopharma company (early 90s) I was QA Manager and did a lot  of supplier qualification audits. I audited a facility for GMPs to make Phase 1 supplies and strongly recommended against them as a supplier.  Just not hygienic, poor controls, etc.  My VP, a know nothing MD PhD overruled me to meet an investor timeline because the facility was lower cost, closer, and  "only going to be used for Phase 1".  Product was to go into AIDS patients.   He submitted the IND to CBER listing that facility as manufacturer of the CTM.  FDA Director called him up (way before 30 days)  and said "you will not use that facility, absolutely not, we will put you on clinical hold". Amazingly he told me I was right. Killed him to do it though.

So, I have seen it happen. If you have the time to wait, why not? Artificial deadlines set by management to please investors who don't care about anything but profits, usually.




------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com

Original Message:
Sent: 23-Mar-2021 09:00
From: Rachel Thornton
Subject: CMC informational amendment to IND

I'll just say that in my 19 years in Reg CMC (vaccines and biologicals), CMC hardly ever gets questions on an IND amendment, and even when we do, they do not result in clinical hold. Even for Ph3 pivotal trials. The fact is, the focus is on the clinical side. At the companies I've worked for, we've always taken a "no waiting" approach. IMO, it is very low risk to not wait. But, of course, if you can afford the time, then it doesn't hurt to wait.

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

Original Message:
Sent: 23-Mar-2021 08:24
From: Ginger Cantor
Subject: CMC informational amendment to IND

So.... has something changed here?  What phase of trials is this in with change of manufacturer?  Maybe you don't HAVE to wait 30 days on CMC but I have really never seen no process changes when something is transferred to a new drug manufacturing facility.

Dependent on what process is moved to a new facility,  (packaging of tablet for example versus full drug product manufacturing or API ).  Know your risks.

And on a side note... becomes more risk as you move into Phase 3 pivotals.


------------------------------
Ginger Cantor, MBA, RAC
Founder/Principal Consultant
Centaur Consulting LLC
River Falls, Wisconsin 54022 USA
715-307-1850
centaurconsultingllc@gmail.com

Original Message:
Sent: 22-Mar-2021 12:52
From: Rachel Thornton
Subject: CMC informational amendment to IND

I agree with those who say no need to wait 30dys for the CMC amendment.

I can see waiting 30dys (or until you hear back) re. the protocol amendment for the new trial, but they don't have to be submitted at the same time and you are unlikely to get questions on the CMC part if it's only a change in manufacturing site (unless you have a history of GMP problems). And, as others said, there's nothing that precludes the Agency from asking for information even after the 30dys. And if you've discussed everything with the Agency beforehand, I really see not purpose in waiting, at least for the CMC part. Clinical considerations are outside my experience, so I can't really advise on that part.

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

Original Message:
Sent: 17-Mar-2021 17:36
From: Anonymous Member
Subject: CMC informational amendment to IND

This message was posted by a user wishing to remain anonymous

With an informational amendment (new manufacturer, little to no process updates) to an IND (transfer of ownership, however), is it expected to wait 30 days to see if FDA has any feedback/ is it customary to wait?  This is slightly different scenario since the sponsor is changing and new sponsor will submit the amendment and a new Ph 2 trial with the new sponsor is starting (within the same division with similar disease state so assuming no new IND which will be verified with the PM.)  Thanks for your input!