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1572 Forms

  • 1.  1572 Forms

    This message was posted by a user wishing to remain anonymous
    Posted 22-Apr-2021 08:59
    This message was posted by a user wishing to remain anonymous

    Dear Forum,

    I am consulting for a company who is conducting a multinational study, and all sites (U.S. and non-U.S) have been submitted to the IND.  However,  for the non-U.S. sites, a 1572 form was not signed.  Instead, the CRO created a form that contained the same information as the 1572 form, except they removed all CFR 21 citations for the non-U.S. sites to sign.
    Based upon the guidance for Sponsors, Clinical Investigators and IRB's, dated June 2010, this does not seem to be the solution.  However, I wanted to ensure I am interpreting the regulation/guidance appropriately.
    Thank you for your help!
    Kind Regards


  • 2.  RE: 1572 Forms

    Posted 22-Apr-2021 10:19
    The IND sponsor should submit a waiver from the requirement in 21 CFR 312.53(c)(1) to obtain a signed investigator statement (Form FDA 1572) from the non-US site investigators to the IND.  The waiver request should include (1)rationale for requesting the waiver; (2)list of non-US sites; and (3) proposed alternative to ensure compliance with FDA regulations.  The waiver request should be submitted before site participation.

    ------------------------------
    Susan White RAC
    Executive Director, Regulatory Affairs
    Kyowa Kirin
    Yardley PA
    United States
    ------------------------------

    Original Message


  • 3.  RE: 1572 Forms

    Posted 23-Apr-2021 07:58
    There are two ways (at least) to handle this scenario. Susan's way is strictly according to the guidance. However, I have also managed this by having the investigator sign a commitment form exactly like you describe but did not submit the investigators to the IND. Then in the clinical study report Appendix 16 section, include a list of investigators and a description of how you assured that the investigator conducted the study according to GCP guidance and FDA regulations. I have done this in 2 NDAs and have not received any negative feedback, including from BIMO inspections of those investigators.

    I would be interested in hearing from other regulatory professionals of recent experience with strictly following the guidance, but when I tried to submit a waiver soon after the guidance came out, the request for additional information from FDA was so onerous that it was not worth it. After all, it is a guidance, and it is not required to obtain a waiver for FDA to accept the foreign data for approval.

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

    Original Message


  • 4.  RE: 1572 Forms

    Posted 25-Apr-2021 20:35
    Hi Glen, 

    Completely similar situation and plan to do what you have suggested and have done in the past at the time of NDA filing. When submitting the US new Investigator information as a protocol amendment, I have in the past included language to indicate that Investigator information for the exUS sites is being collected and being filed in the TMF but not submitted.

    ------------------------------
    Aparna Donti Geddam
    AD, Regulatory Affairs
    PTC Therapeutics
    Green Brook NJ
    United States
    ------------------------------

    Original Message


  • 5.  RE: 1572 Forms

    Posted 26-Apr-2021 12:24
    Edited by Aziz Alam 26-Apr-2021 12:24
    From a regulatory strategy perspective, I have had more streamlined success with Glen's approach regarding providing the investigator descriptions vs. filing for a waiver. I can confirm I have gone through at least one BIMO inspection and NDA, using this approach for Ex-US investigators, and this has not been an issue. 

    Best,
    ------------------------------
    Aziz Alam
    Sr. Director, Regulatory Affairs
    Kinnate Biopharma, Inc.
    San Diego, CA
    United States
    ------------------------------


    Original Message


  • 6.  RE: 1572 Forms

    Posted 20-May-2021 15:53
    I would like to understand why a sponsor would chose to conducted non-US sites under an IND, even in a multinational study with US sites.

    The 2010 FDA guidance FAQ (Q14) states a multinational study may include domestic sites under the IND and foreign sites not under the IND. Therefore, investigators at non-US sites (foreign clinical sites) participating in a single multinational study protocol that includes participating investigators at US sites (domestic sites) do not need to be conducted under an IND. A single IND study may have US domestic sites conducted under the IND (with signed 1572 and investigator information submitted to the IND) and foreign "non-IND" clinical sites not under the IND (no 1572 and/or investigator information submitted to the IND). Accordingly, a sponsor of a multinational study needs only to have US investigators sign 1572s and submit US investigator information to the IND.  

    For the data from the foreign "non-IND" clinical sites to be accepted in a US marketing application, the foreign "non-IND" clinical sites must meet the requirements of 21 CFR 312.120 and/or the sponsor request and be granted specific waivers from the requirements of 21 CFR 312.120. Also, safety reporting requirements 21 CFR 312.32 apply regardless of whether foreign clinical sites are conducted under the IND or not.

    A great deal of time and effort goes into collecting non-US signed 1572s, submitting investigator information and/or requesting waivers for foreign sites, when this effort does not seem necessary. Can anyone explain why they chose to conduct non-US sites under an IND?



    ------------------------------
    Amy Van Andel
    Vice President, Regulatory Affairs
    Monroe CT
    United States
    ------------------------------

    Original Message


  • 7.  RE: 1572 Forms

    Posted 21-May-2021 08:36
    Here's a timely update from FDA to their FAQ around 1572: https://www.fda.gov/media/148810/download

    This seems to address a few of the questions in this thread around 1572s for non-US sites. And it also provides for both options: 1) request a signature waiver for non-US site under the IND and 2) not including the non-US site under the IND. 
    Hope that helps.



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    Anna Sedello, PhD, RAC
    Director of Regulatory Affairs
    Atreca Inc., San Carlos, CA, USA
    ------------------------------

    Original Message


  • 8.  RE: 1572 Forms

    Posted 21-May-2021 09:34
    On May 20, FDA issued a Draft update to the guidance on the Form 1572.  In this draft it updates it explanation on the use of the Form 1572 for sites outside of US and what to do when sites can't/won't sign the form outside of US.  It provides an updated explanation on how to proceed in this regard.  Check the FDA web page for details.

    ------------------------------
    Michael Hamrell, Ph.D., RAC, FRAPS
    MORIAH Consultants
    Huntington Beach CA
    United States
    ------------------------------

    Original Message


  • 9.  RE: 1572 Forms

    Posted 21-May-2021 11:16
    I have reviewed the May 2021 draft update to the FAQs and they do not update Q14, which states that a single multinational study may include domestic sites under the IND and foreign sites not under the IND. Accordingly, a sponsor of a multinational study with US sites needs only to have US investigators sign 1572s and submit US investigator information to the IND. Due to time and effort that goes into collecting non-US signed 1572s, submitting investigator information and/or requesting waivers for foreign sites, I am curious as to why a sponsor would chose to conduct non-US sites under an IND?

    ------------------------------
    Amy Van Andel
    Vice President, Regulatory Affairs
    Molecular Templates, Inc
    United States
    amyva314@gmail.com
    ------------------------------

    Original Message


  • 10.  RE: 1572 Forms

    Posted 21-May-2021 11:30
    I would agree.  However, there are often business and strategic reasons that companies wish to have all sites under the IND, including non-US sites.  Part of this is historical considerations that signing the form will somehow guarantee compliance with GCP.  If all sites are following GCP as defined by ICH, then the presence or absence of a signed Form 1572 is not critical.  Most companies require a signed commitment in contracts and protocol signature pages to follow GCP, so the PI is already agreeing elsewhere to comply with proper procedures.

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    Michael Hamrell, Ph.D., RAC, FRAPS
    MORIAH Consultants
    Huntington Beach CA
    United States
    ------------------------------

    Original Message


  • 11.  RE: 1572 Forms

    This message was posted by a user wishing to remain anonymous
    Posted 21-May-2021 16:48
    This message was posted by a user wishing to remain anonymous

    Strategically I'd favor including non-US sites under an IND and I wouldn't consider collecting non-US 1572s as waste of time and effort if the trial is a pivotal registration trial and specifically for non-orphan and general therapeutic area like CNS, Endocrinology, cardiovascular etc......Else the FDA wouldn't have given options!
    Original Message


  • 12.  RE: 1572 Forms

    Posted 21-May-2021 11:36
    FDA just posted the following FAQ related to form 1572 which addresses some of your questions.
    As suggested by the others, the non-US sites participating in a multinational trial don't need to conduct the trial under a US IND.  Only the US sites operate under IND. 


    ------------------------------
    Chaoyu Xie, Ph.D
    VP, Regulatory Affairs
    Qilu Pharmaceutical
    China
    ------------------------------

    Original Message


  • 13.  RE: 1572 Forms

    Posted 24-May-2021 11:35
    I agree that the FDA makes it clear that non US investigators of a multinational trial with US-sites do not need to be conducted under an IND. That is why I am curious why sponsors choose to submit non-US sites and/or obtain a waiver. I am aware of fully successfully pivotal multinational trials with US sites without any non-US sites being conducted under and IND - no issues with FDA inspections, at least none that would have been solved with a signed 1572 and/or waiver.

    ------------------------------
    Amy Van Andel
    Vice President, Regulatory Affairs
    Molecular Templates, Inc
    United States
    amyva314@gmail.com
    ------------------------------

    Original Message


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