Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Dear Forum,

apparently select countries in Europe are starting to refuse to sign Form 1572. Does anyone have experience on how to get a waiver from FDA for an affected IND?

many thanks!

Per 21 CFR 312.10, you can request a waiver from the requirement in 21 CFR 312.53(c)(1) to obtain a signed Form 1572 for non-US sites/investigators.  You can do this by submitting a cover letter containing the waiver request to your IND.  You'll need to provide the rationale for why you are making the request.  We've also included with the request a substitute 1572-like form that modifies/omits the statements agreeing to adhere to US-specific regulations so that we can collect all the same info as the Form 1572 and non-US investigators should be able to sign the substitute form (but I don't think the substitute form is required as part of your waiver request).

In my (limited) experience with these waiver requests, the FDA has come back and asked us for a specific list of investigators who cannot sign the 1572 and the exact reason why each investigator cannot sign it.  This was for investigators in Canada, where some investigators actually can sign Form 1572.  I'm not sure whether the FDA would push back so hard on a 1572 waiver request for European investigators.

------------------------------
Marissa Berry, Ph.D., RAC
Manager, Global Regulatory Affairs
Cary, NC
United States
------------------------------

Original Message:
Sent: 09-Jul-2019 11:52
From: Anonymous Member
Subject: how to deal with Europe's not signing 1572?

This message was posted by a user wishing to remain anonymous

Dear Forum,

apparently select countries in Europe are starting to refuse to sign Form 1572. Does anyone have experience on how to get a waiver from FDA for an affected IND?

many thanks!

Hi Marissa:

In your experience, how long did it take for FDA to respond to your waiver request?  What was the complete timeline (from submission, to receipt of waiver)?

Thanks so much!
Lisa

------------------------------
Lisa Drucker
Montville NJ
United States
------------------------------

Original Message:
Sent: 10-Jul-2019 09:43
From: Marissa Berry
Subject: how to deal with Europe's not signing 1572?

Per 21 CFR 312.10, you can request a waiver from the requirement in 21 CFR 312.53(c)(1) to obtain a signed Form 1572 for non-US sites/investigators.  You can do this by submitting a cover letter containing the waiver request to your IND.  You'll need to provide the rationale for why you are making the request.  We've also included with the request a substitute 1572-like form that modifies/omits the statements agreeing to adhere to US-specific regulations so that we can collect all the same info as the Form 1572 and non-US investigators should be able to sign the substitute form (but I don't think the substitute form is required as part of your waiver request).

In my (limited) experience with these waiver requests, the FDA has come back and asked us for a specific list of investigators who cannot sign the 1572 and the exact reason why each investigator cannot sign it.  This was for investigators in Canada, where some investigators actually can sign Form 1572.  I'm not sure whether the FDA would push back so hard on a 1572 waiver request for European investigators.

------------------------------
Marissa Berry, Ph.D., RAC
Manager, Global Regulatory Affairs
Cary, NC
United States

Original Message:
Sent: 09-Jul-2019 11:52
From: Anonymous Member
Subject: how to deal with Europe's not signing 1572?

This message was posted by a user wishing to remain anonymous

Dear Forum,

apparently select countries in Europe are starting to refuse to sign Form 1572. Does anyone have experience on how to get a waiver from FDA for an affected IND?

many thanks!

Hi Lisa,

It took the FDA just a little over 2 weeks after our initial waiver request to come back with their first request for information (a list of the investigators who could not sign the 1572).  We responded via e-mail the same day and also to the IND about 2 weeks after the RFI was received.  Then it took the FDA another two weeks after our IND submission (about a month after our e-mail) to come back with their second request for information (the specific reason why each investigator could not sign the 1572).  At that point, we bounced the question to the CRO who was assisting with our study, and after some digging they found out that the non-US investigators in our study actually could sign the 1572, so we ended up withdrawing our waiver request and apologizing for the inconvenience.  (Lesson learned there - double check that a 1572 waiver request is actually necessary before letting your CRO talk you into submitting it)

All things said and done, it seemed like it took the FDA roughly 2 weeks to respond after each official submission to the IND regarding our waiver request.  Depending on how much info you provide in your initial request and how long it takes you to respond to any requests for information, it seemed like the whole process could be done in a month or do.  But, that was my one experience with one particular division.  I'm sure things could be different depending on division.

Cheers,
Marissa

------------------------------
Marissa Berry, Ph.D., RAC
Manager, Global Regulatory Affairs
Cary, NC
United States
------------------------------

Original Message:
Sent: 10-Jul-2019 15:56
From: Lisa Drucker
Subject: how to deal with Europe's not signing 1572?

Hi Marissa:

In your experience, how long did it take for FDA to respond to your waiver request?  What was the complete timeline (from submission, to receipt of waiver)?

Thanks so much!
Lisa

------------------------------
Lisa Drucker
Montville NJ
United States

Original Message:
Sent: 10-Jul-2019 09:43
From: Marissa Berry
Subject: how to deal with Europe's not signing 1572?

Per 21 CFR 312.10, you can request a waiver from the requirement in 21 CFR 312.53(c)(1) to obtain a signed Form 1572 for non-US sites/investigators.  You can do this by submitting a cover letter containing the waiver request to your IND.  You'll need to provide the rationale for why you are making the request.  We've also included with the request a substitute 1572-like form that modifies/omits the statements agreeing to adhere to US-specific regulations so that we can collect all the same info as the Form 1572 and non-US investigators should be able to sign the substitute form (but I don't think the substitute form is required as part of your waiver request).

In my (limited) experience with these waiver requests, the FDA has come back and asked us for a specific list of investigators who cannot sign the 1572 and the exact reason why each investigator cannot sign it.  This was for investigators in Canada, where some investigators actually can sign Form 1572.  I'm not sure whether the FDA would push back so hard on a 1572 waiver request for European investigators.

------------------------------
Marissa Berry, Ph.D., RAC
Manager, Global Regulatory Affairs
Cary, NC
United States

Original Message:
Sent: 09-Jul-2019 11:52
From: Anonymous Member
Subject: how to deal with Europe's not signing 1572?

This message was posted by a user wishing to remain anonymous

Dear Forum,

apparently select countries in Europe are starting to refuse to sign Form 1572. Does anyone have experience on how to get a waiver from FDA for an affected IND?

many thanks!

My experience with EU is that countries have started specifically prohibit signing the 1572 since they cannot follow our regulations. What we are doing is to create a form that states all the requirements for GCP according to their local laws and just not mentioning FDA regulations. They have no problem signing that form. And, we do not submit them to the IND. We will include them when the NDA/BLA is submitted with a statement saying they study was conducted under GCP. My only experience with requesting a waiver has been to get an onerous request from FDA for all kinds of information.

------------------------------
Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
Jersey City NJ
United States
------------------------------

Original Message:
Sent: 10-Jul-2019 09:43
From: Marissa Berry
Subject: how to deal with Europe's not signing 1572?

Per 21 CFR 312.10, you can request a waiver from the requirement in 21 CFR 312.53(c)(1) to obtain a signed Form 1572 for non-US sites/investigators.  You can do this by submitting a cover letter containing the waiver request to your IND.  You'll need to provide the rationale for why you are making the request.  We've also included with the request a substitute 1572-like form that modifies/omits the statements agreeing to adhere to US-specific regulations so that we can collect all the same info as the Form 1572 and non-US investigators should be able to sign the substitute form (but I don't think the substitute form is required as part of your waiver request).

In my (limited) experience with these waiver requests, the FDA has come back and asked us for a specific list of investigators who cannot sign the 1572 and the exact reason why each investigator cannot sign it.  This was for investigators in Canada, where some investigators actually can sign Form 1572.  I'm not sure whether the FDA would push back so hard on a 1572 waiver request for European investigators.

------------------------------
Marissa Berry, Ph.D., RAC
Manager, Global Regulatory Affairs
Cary, NC
United States

Original Message:
Sent: 09-Jul-2019 11:52
From: Anonymous Member
Subject: how to deal with Europe's not signing 1572?

This message was posted by a user wishing to remain anonymous

Dear Forum,

apparently select countries in Europe are starting to refuse to sign Form 1572. Does anyone have experience on how to get a waiver from FDA for an affected IND?

many thanks!

Thank you, Glen for your quick response!

------------------------------
Lisa Drucker
Montville NJ
United States
------------------------------

Original Message:
Sent: 10-Jul-2019 15:58
From: Glen Park
Subject: how to deal with Europe's not signing 1572?

My experience with EU is that countries have started specifically prohibit signing the 1572 since they cannot follow our regulations. What we are doing is to create a form that states all the requirements for GCP according to their local laws and just not mentioning FDA regulations. They have no problem signing that form. And, we do not submit them to the IND. We will include them when the NDA/BLA is submitted with a statement saying they study was conducted under GCP. My only experience with requesting a waiver has been to get an onerous request from FDA for all kinds of information.

------------------------------
Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
Jersey City NJ
United States

Original Message:
Sent: 10-Jul-2019 09:43
From: Marissa Berry
Subject: how to deal with Europe's not signing 1572?

Per 21 CFR 312.10, you can request a waiver from the requirement in 21 CFR 312.53(c)(1) to obtain a signed Form 1572 for non-US sites/investigators.  You can do this by submitting a cover letter containing the waiver request to your IND.  You'll need to provide the rationale for why you are making the request.  We've also included with the request a substitute 1572-like form that modifies/omits the statements agreeing to adhere to US-specific regulations so that we can collect all the same info as the Form 1572 and non-US investigators should be able to sign the substitute form (but I don't think the substitute form is required as part of your waiver request).

In my (limited) experience with these waiver requests, the FDA has come back and asked us for a specific list of investigators who cannot sign the 1572 and the exact reason why each investigator cannot sign it.  This was for investigators in Canada, where some investigators actually can sign Form 1572.  I'm not sure whether the FDA would push back so hard on a 1572 waiver request for European investigators.

------------------------------
Marissa Berry, Ph.D., RAC
Manager, Global Regulatory Affairs
Cary, NC
United States

Original Message:
Sent: 09-Jul-2019 11:52
From: Anonymous Member
Subject: how to deal with Europe's not signing 1572?

This message was posted by a user wishing to remain anonymous

Dear Forum,

apparently select countries in Europe are starting to refuse to sign Form 1572. Does anyone have experience on how to get a waiver from FDA for an affected IND?

many thanks!

Some OUS investigators are willing to sign a 1572, but many are not and that is increasing in my recent experience.  The 1572 is a convenient document to collect certain information, but it also commits the investigator to follow US FDA requirements, which may or may not be consistent with local regulations. In my former company, we created a separate document to collect the same information from the 1572 and included that information as an OUS addendum when the CSR was completed.

------------------------------
Beth Weinberg
Regulatory Affairs Lead
Carmel IN
United States
------------------------------

Original Message:
Sent: 10-Jul-2019 09:43
From: Marissa Berry
Subject: how to deal with Europe's not signing 1572?

Per 21 CFR 312.10, you can request a waiver from the requirement in 21 CFR 312.53(c)(1) to obtain a signed Form 1572 for non-US sites/investigators.  You can do this by submitting a cover letter containing the waiver request to your IND.  You'll need to provide the rationale for why you are making the request.  We've also included with the request a substitute 1572-like form that modifies/omits the statements agreeing to adhere to US-specific regulations so that we can collect all the same info as the Form 1572 and non-US investigators should be able to sign the substitute form (but I don't think the substitute form is required as part of your waiver request).

In my (limited) experience with these waiver requests, the FDA has come back and asked us for a specific list of investigators who cannot sign the 1572 and the exact reason why each investigator cannot sign it.  This was for investigators in Canada, where some investigators actually can sign Form 1572.  I'm not sure whether the FDA would push back so hard on a 1572 waiver request for European investigators.

------------------------------
Marissa Berry, Ph.D., RAC
Manager, Global Regulatory Affairs
Cary, NC
United States

Original Message:
Sent: 09-Jul-2019 11:52
From: Anonymous Member
Subject: how to deal with Europe's not signing 1572?

This message was posted by a user wishing to remain anonymous

Dear Forum,

apparently select countries in Europe are starting to refuse to sign Form 1572. Does anyone have experience on how to get a waiver from FDA for an affected IND?

many thanks!

There is a FDA "Information Sheet" FAQ that addresses 1572's.  See https://www.fda.gov/media/78830/download

You are not obligated to conduct ex-US sites in a multi-national clinical trial under a US IND. See Q 14 in the Information Sheet.

My advice: conduct the ex-US sites under their respective CTAs and do not submit the investigators to the IND.  This approach eliminates the foreign compliance risks related subjecting foreign investigators to US regulations.  No waiver is needed because the foreign sites are not subject to the IND.

------------------------------
Michelle McGuinness
Consultant - Quality Assurance, Regulatory Affairs & Commercial Compliance
Glenmoore PA
United States
------------------------------

Original Message:
Sent: 09-Jul-2019 11:52
From: Anonymous Member
Subject: how to deal with Europe's not signing 1572?

This message was posted by a user wishing to remain anonymous

Dear Forum,

apparently select countries in Europe are starting to refuse to sign Form 1572. Does anyone have experience on how to get a waiver from FDA for an affected IND?

many thanks!