Regulatory Open Forum

Hi everyone,

Did some initial research on CFRs or guidances that cover this topic, but I am still not satisfied.

If anyone has any recommendations based on guidances, CFRs, or past experiences, then I would be really grateful if it could be shared with me.

Background:
Approvals sometimes may come with a PMR/PMC where a protocol must be submitted. I have had a prior experience where the FDA explicitly asked us to submit said protocol to the IND with a cross-reference letter referencing said submission to the marketing application.  In my current situation, the reverse is asked (i.e. submit the protocol to the marketing application and a cross-reference to the IND). 

Question 1:
Would you submit the CSR for the completed study/protocol to where the study/protocol was submitted to?

Additional Context:
From my previous experiences, I was trained that it was good practice to keep the IND as the source of study information, so CSRs were always sent to the IND. It should be noted that CFRs 312.20 and 314.50 state that information previously submitted need not be resubmitted but referenced (hopefully I'm not using this in the incorrect context). What I struggle to grasp was why regulatory leads I've worked with would resubmit information as part of a marketing application rather than "reference" said information with some type of cross-referencing (e.g. M1.4.4).

Question 2:
Is there a hard rule on the submission of CSRs to the IND vs the marketing application?

Question 3:
Has anyone had experiences where they've "referenced" information previously submitted (my specific focus is on reports -- specifically CSRs) as part of a marketing application and how exactly did you use M1.4.4 to accomplish this? 

Question 4:
Has anyone had case where all CSRs were submitted to their marketing application and not to their IND for whatever reason?

------------------------------
Samuel Christopher Bonilla
Los Angeles CA
United States
------------------------------

Complicated question(s) :-)

It is also my experience that new protocols that needed to be conducted under an IND if the population or indication were not covered by the marketing approval were submitted to the IND.  I could see a preference on the part of FDA for a protocol and CSR that would ultimately be an sNDA to be under an IND until the sNDA was submitted.  However, if it was a study that would not change labeling but was part of a PMC/PMR that it be submitted to the NDA.

Regarding 1.4.4 for cross-referencing, it is my understanding that most eCTD software (maybe all?) cannot cross-reference between applications and that is where this Module comes into play.  I have not done that between an IND and NDA, but between two INDs with different formulations (oral and IV).  

My fallback is always to ask the PM where they want it submitted and not try to parse the rationale too finely.

------------------------------
Glen Park
Scynexis, Inc.
Jersey City NJ
United States
------------------------------

Original Message:
Sent: 17-Jan-2018 23:03
From: Samuel Christopher Bonilla
Subject: FDA -- Referencing between an IND and Marketing Application

Hi everyone,

Did some initial research on CFRs or guidances that cover this topic, but I am still not satisfied.

If anyone has any recommendations based on guidances, CFRs, or past experiences, then I would be really grateful if it could be shared with me.

Background:
Approvals sometimes may come with a PMR/PMC where a protocol must be submitted. I have had a prior experience where the FDA explicitly asked us to submit said protocol to the IND with a cross-reference letter referencing said submission to the marketing application.  In my current situation, the reverse is asked (i.e. submit the protocol to the marketing application and a cross-reference to the IND).

Question 1:
Would you submit the CSR for the completed study/protocol to where the study/protocol was submitted to?

Additional Context:
From my previous experiences, I was trained that it was good practice to keep the IND as the source of study information, so CSRs were always sent to the IND. It should be noted that CFRs 312.20 and 314.50 state that information previously submitted need not be resubmitted but referenced (hopefully I'm not using this in the incorrect context). What I struggle to grasp was why regulatory leads I've worked with would resubmit information as part of a marketing application rather than "reference" said information with some type of cross-referencing (e.g. M1.4.4).

Question 2:
Is there a hard rule on the submission of CSRs to the IND vs the marketing application?

Question 3:
Has anyone had experiences where they've "referenced" information previously submitted (my specific focus is on reports -- specifically CSRs) as part of a marketing application and how exactly did you use M1.4.4 to accomplish this?

Question 4:
Has anyone had case where all CSRs were submitted to their marketing application and not to their IND for whatever reason?

------------------------------
Samuel Christopher Bonilla
Los Angeles CA
United States
------------------------------

Thanks Glen!

------------------------------
Samuel Christopher Bonilla
Los Angeles CA
United States
------------------------------

Original Message:
Sent: 18-Jan-2018 08:25
From: Glen Park
Subject: FDA -- Referencing between an IND and Marketing Application

Complicated question(s) :-)

It is also my experience that new protocols that needed to be conducted under an IND if the population or indication were not covered by the marketing approval were submitted to the IND.  I could see a preference on the part of FDA for a protocol and CSR that would ultimately be an sNDA to be under an IND until the sNDA was submitted.  However, if it was a study that would not change labeling but was part of a PMC/PMR that it be submitted to the NDA.

Regarding 1.4.4 for cross-referencing, it is my understanding that most eCTD software (maybe all?) cannot cross-reference between applications and that is where this Module comes into play.  I have not done that between an IND and NDA, but between two INDs with different formulations (oral and IV).

My fallback is always to ask the PM where they want it submitted and not try to parse the rationale too finely.

------------------------------
Glen Park
Scynexis, Inc.
Jersey City NJ
United States

Original Message:
Sent: 17-Jan-2018 23:03
From: Samuel Christopher Bonilla
Subject: FDA -- Referencing between an IND and Marketing Application

Hi everyone,

Did some initial research on CFRs or guidances that cover this topic, but I am still not satisfied.

If anyone has any recommendations based on guidances, CFRs, or past experiences, then I would be really grateful if it could be shared with me.

Background:
Approvals sometimes may come with a PMR/PMC where a protocol must be submitted. I have had a prior experience where the FDA explicitly asked us to submit said protocol to the IND with a cross-reference letter referencing said submission to the marketing application.  In my current situation, the reverse is asked (i.e. submit the protocol to the marketing application and a cross-reference to the IND).

Question 1:
Would you submit the CSR for the completed study/protocol to where the study/protocol was submitted to?

Additional Context:
From my previous experiences, I was trained that it was good practice to keep the IND as the source of study information, so CSRs were always sent to the IND. It should be noted that CFRs 312.20 and 314.50 state that information previously submitted need not be resubmitted but referenced (hopefully I'm not using this in the incorrect context). What I struggle to grasp was why regulatory leads I've worked with would resubmit information as part of a marketing application rather than "reference" said information with some type of cross-referencing (e.g. M1.4.4).

Question 2:
Is there a hard rule on the submission of CSRs to the IND vs the marketing application?

Question 3:
Has anyone had experiences where they've "referenced" information previously submitted (my specific focus is on reports -- specifically CSRs) as part of a marketing application and how exactly did you use M1.4.4 to accomplish this?

Question 4:
Has anyone had case where all CSRs were submitted to their marketing application and not to their IND for whatever reason?

------------------------------
Samuel Christopher Bonilla
Los Angeles CA
United States
------------------------------