Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hello All,

Our company recently submitted a phase I IND for a monoclonal antibody. My questions are as follows:

1) After how many days of submission, will we receive requests or questions from the FDA if any?
2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call? 
3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?
4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?
5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it? 

Thank you.

Hello anonymous,

1) After how many days of submission, will we receive requests or questions from the FDA if any?  

Question timing could be within a week or so if the review identifies major gaps in the submission that could prevent a complete review. Otherwise, they would typically come in weeks 3 and 4.

2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?

Email is the most likely channel. It has been a long time since questions/requests were sent by a phone call or facsimile. An unscheduled phone call would now typically come if there is a major issue that could result in a clinical hold. In my experience, such a call from the RPM would be to notify the company that such an issue has been identified and to schedule a call with the review team and company experts.

3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?

If you satisfactorily address their concerns within the 30-day review period, you will not get a "clinical hold" notice. A clinical hold would be imposed only if there are concerns that cannot be resolved within the 30 days.

4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?

Just make sure the team is available and prepared to respond quickly, and are knowledgeable about the regulations, the product, and the IND content.

5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

No. First, such an inspection could not be performed in the 30-day review period. Second, if there were questions about the ability of the firm to manufacture a quality product for Phase 1, based on the content of the IND quality section, the only option would be a clinical hold until the questions are resolved.

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

Original Message:
Sent: 28-Nov-2021 23:21
From: Anonymous Member
Subject: IND - 30 day review process - possible audit

This message was posted by a user wishing to remain anonymous

Hello All,

Our company recently submitted a phase I IND for a monoclonal antibody. My questions are as follows:

1) After how many days of submission, will we receive requests or questions from the FDA if any?
2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?
3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?
4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?
5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

Thank you.

This message was posted by a user wishing to remain anonymous

Hello,

Just curious how many IND submissions (what percentage) will pass without any questions from FDA. Is the percentage very different for big pharma and small biotech?
Original Message:
Sent: 30-Nov-2021 04:07
From: Glen Park
Subject: IND - 30 day review process - possible audit

Hello anonymous,

1) After how many days of submission, will we receive requests or questions from the FDA if any?

Question timing could be within a week or so if the review identifies major gaps in the submission that could prevent a complete review. Otherwise, they would typically come in weeks 3 and 4.

2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?

Email is the most likely channel. It has been a long time since questions/requests were sent by a phone call or facsimile. An unscheduled phone call would now typically come if there is a major issue that could result in a clinical hold. In my experience, such a call from the RPM would be to notify the company that such an issue has been identified and to schedule a call with the review team and company experts.

3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?

If you satisfactorily address their concerns within the 30-day review period, you will not get a "clinical hold" notice. A clinical hold would be imposed only if there are concerns that cannot be resolved within the 30 days.

4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?

Just make sure the team is available and prepared to respond quickly, and are knowledgeable about the regulations, the product, and the IND content.

5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

No. First, such an inspection could not be performed in the 30-day review period. Second, if there were questions about the ability of the firm to manufacture a quality product for Phase 1, based on the content of the IND quality section, the only option would be a clinical hold until the questions are resolved.

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

Original Message:
Sent: 28-Nov-2021 23:21
From: Anonymous Member
Subject: IND - 30 day review process - possible audit

This message was posted by a user wishing to remain anonymous

Hello All,

Our company recently submitted a phase I IND for a monoclonal antibody. My questions are as follows:

1) After how many days of submission, will we receive requests or questions from the FDA if any?
2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?
3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?
4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?
5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

Thank you.

My personal experience, all small biotech, is 10-20% will clear without any requests.

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

Original Message:
Sent: 30-Nov-2021 18:53
From: Anonymous Member
Subject: IND - 30 day review process - possible audit

This message was posted by a user wishing to remain anonymous

Hello,

Just curious how many IND submissions (what percentage) will pass without any questions from FDA. Is the percentage very different for big pharma and small biotech?
Original Message:
Sent: 30-Nov-2021 04:07
From: Glen Park
Subject: IND - 30 day review process - possible audit

Hello anonymous,

1) After how many days of submission, will we receive requests or questions from the FDA if any?

Question timing could be within a week or so if the review identifies major gaps in the submission that could prevent a complete review. Otherwise, they would typically come in weeks 3 and 4.

2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?

Email is the most likely channel. It has been a long time since questions/requests were sent by a phone call or facsimile. An unscheduled phone call would now typically come if there is a major issue that could result in a clinical hold. In my experience, such a call from the RPM would be to notify the company that such an issue has been identified and to schedule a call with the review team and company experts.

3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?

If you satisfactorily address their concerns within the 30-day review period, you will not get a "clinical hold" notice. A clinical hold would be imposed only if there are concerns that cannot be resolved within the 30 days.

4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?

Just make sure the team is available and prepared to respond quickly, and are knowledgeable about the regulations, the product, and the IND content.

5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

No. First, such an inspection could not be performed in the 30-day review period. Second, if there were questions about the ability of the firm to manufacture a quality product for Phase 1, based on the content of the IND quality section, the only option would be a clinical hold until the questions are resolved.

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

Original Message:
Sent: 28-Nov-2021 23:21
From: Anonymous Member
Subject: IND - 30 day review process - possible audit

This message was posted by a user wishing to remain anonymous

Hello All,

Our company recently submitted a phase I IND for a monoclonal antibody. My questions are as follows:

1) After how many days of submission, will we receive requests or questions from the FDA if any?
2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?
3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?
4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?
5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

Thank you.

This message was posted by a user wishing to remain anonymous

Original poster here. Thank you for the reply. One more question: how many days (hours) do companies have after receiving FDA's information request?
Original Message:
Sent: 30-Nov-2021 04:07
From: Glen Park
Subject: IND - 30 day review process - possible audit

Hello anonymous,

1) After how many days of submission, will we receive requests or questions from the FDA if any?

Question timing could be within a week or so if the review identifies major gaps in the submission that could prevent a complete review. Otherwise, they would typically come in weeks 3 and 4.

2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?

Email is the most likely channel. It has been a long time since questions/requests were sent by a phone call or facsimile. An unscheduled phone call would now typically come if there is a major issue that could result in a clinical hold. In my experience, such a call from the RPM would be to notify the company that such an issue has been identified and to schedule a call with the review team and company experts.

3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?

If you satisfactorily address their concerns within the 30-day review period, you will not get a "clinical hold" notice. A clinical hold would be imposed only if there are concerns that cannot be resolved within the 30 days.

4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?

Just make sure the team is available and prepared to respond quickly, and are knowledgeable about the regulations, the product, and the IND content.

5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

No. First, such an inspection could not be performed in the 30-day review period. Second, if there were questions about the ability of the firm to manufacture a quality product for Phase 1, based on the content of the IND quality section, the only option would be a clinical hold until the questions are resolved.

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

Original Message:
Sent: 28-Nov-2021 23:21
From: Anonymous Member
Subject: IND - 30 day review process - possible audit

This message was posted by a user wishing to remain anonymous

Hello All,

Our company recently submitted a phase I IND for a monoclonal antibody. My questions are as follows:

1) After how many days of submission, will we receive requests or questions from the FDA if any?
2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?
3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?
4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?
5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

Thank you.

It depends on the time the request comes in the review cycle and its importance. I have received requests, such as changes in the protocol for safety monitoring issues on Day 29 with a deadline for response the next day. Some requests that are mainly box checking exercises you may get earlier in the review cycle and have several days to respond. It is hard, therefore, to define a standard. It is unlike some authorities where they may issue a request and stop the review until you respond. The earlier the request in the cycle, the better chance you will have to negotiate a later deadline.

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

Original Message:
Sent: 01-Dec-2021 11:10
From: Anonymous Member
Subject: IND - 30 day review process - possible audit

This message was posted by a user wishing to remain anonymous

Original poster here. Thank you for the reply. One more question: how many days (hours) do companies have after receiving FDA's information request?
Original Message:
Sent: 30-Nov-2021 04:07
From: Glen Park
Subject: IND - 30 day review process - possible audit

Hello anonymous,

1) After how many days of submission, will we receive requests or questions from the FDA if any?

Question timing could be within a week or so if the review identifies major gaps in the submission that could prevent a complete review. Otherwise, they would typically come in weeks 3 and 4.

2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?

Email is the most likely channel. It has been a long time since questions/requests were sent by a phone call or facsimile. An unscheduled phone call would now typically come if there is a major issue that could result in a clinical hold. In my experience, such a call from the RPM would be to notify the company that such an issue has been identified and to schedule a call with the review team and company experts.

3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?

If you satisfactorily address their concerns within the 30-day review period, you will not get a "clinical hold" notice. A clinical hold would be imposed only if there are concerns that cannot be resolved within the 30 days.

4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?

Just make sure the team is available and prepared to respond quickly, and are knowledgeable about the regulations, the product, and the IND content.

5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

No. First, such an inspection could not be performed in the 30-day review period. Second, if there were questions about the ability of the firm to manufacture a quality product for Phase 1, based on the content of the IND quality section, the only option would be a clinical hold until the questions are resolved.

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

Original Message:
Sent: 28-Nov-2021 23:21
From: Anonymous Member
Subject: IND - 30 day review process - possible audit

This message was posted by a user wishing to remain anonymous

Hello All,

Our company recently submitted a phase I IND for a monoclonal antibody. My questions are as follows:

1) After how many days of submission, will we receive requests or questions from the FDA if any?
2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?
3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?
4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?
5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

Thank you.

This message was posted by a user wishing to remain anonymous

Hold related (both partial & full clinical/CMC hold) questions, if any, will be sent before 30 days to respond (the letter/message sent mostly via email will provide all the details).
Clinical hold in general can be placed anytime so don't think  that this is only during 30 day review period! FDA will let you know if their hold related questions are adequately answered around 30th or few days later. Safe to proceed letter, mostly emailed, would also indicate that your hold related questions are adequately addressed!
Original Message:
Sent: 28-Nov-2021 23:21
From: Anonymous Member
Subject: IND - 30 day review process - possible audit

This message was posted by a user wishing to remain anonymous

Hello All,

Our company recently submitted a phase I IND for a monoclonal antibody. My questions are as follows:

1) After how many days of submission, will we receive requests or questions from the FDA if any?
2) What channel will the FDA use for such requests or questions? Email? a scheduled/unscheduled Phone call?
3) If the FDA sends us requests prior to the 30-day review period, and we are able to address their concerns before the 30-day ends, will we still get the "clinical hold" notice?
4) How do companies prepare for potential questions and requests from the FDA (especially for phase I)?
5) For phase I IND submission, does FDA conduct an audit for the manufacturer? If so, how should we prepare for it?

Thank you.