Regulatory Open Forum

 View Only

  • 1.  IND Effective date when IND is on Clinical hold during 30 day review

    This message was posted by a user wishing to remain anonymous
    Posted 10-Apr-2019 19:20
    This message was posted by a user wishing to remain anonymous

    Hello, 
    can someone please confirm that an IND is still considered active and in effect even though the IND is place on clinical hold during the 30 day review period? 
    while the IND is on hold in the US, if the trial is active elsewhere in the world, are we required to submit any safety reports to the on Hold IND? 

    Also, for the purpose of Annual reporting requirement, what would be the anniversary date? is it the 30 days after the clinical hold is lifted or when we are notified the clinical study may proceed or is it something else? 

    please provide any source for your advice if possible so keep them for future reference. 

    thank you in advance.


  • 2.  RE: IND Effective date when IND is on Clinical hold during 30 day review

    Posted 11-Apr-2019 09:02
    Hello Anonymous,

    It is not clear from you question whether the clinical hold was (1) imposed during the initial 30-day review period of an original IND or (2) the IND was already active when the hold was imposed.

    For condition (1), the IND is not yet active and there would be no requirement to submit a safety report, but FDA should be informed of the safety report. The timing may depend on the timing of the Complete Response to the clinical hold. It would be irresponsible, in my opinion, to not inform FDA of a safety report as part of the clinical hold process.

    For condition (2), the IND is active and safety reports need to be submitted to an active IND regardless of whether it is on clinical hold.

    Unfortunately, as far as a specific reference that would support this advice, I first bring your attention to 21 CFR 312.50 on General Responsibilities of a Sponsor to ensure "that FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the drug;" 21 CFR 312.32(c)(1)(ii) IND safety reporting "The sponsor must report any findings from epidemiological studies, pooled analysis of multiple studies, or clinical studies (other than those reported under paragraph (c)(1)(i) of this section), whether or not conducted under an IND;" and to the fundamental regulations in 21 CFR 312.42 (clinical holds).

    The Annual report anniversary date is the date that the IND becomes active, which under condition (1) would be the date that the clinical hold is formerly lifted (study may proceed), or under condition (2) the original IND effective date.


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

    Original Message


  • 3.  RE: IND Effective date when IND is on Clinical hold during 30 day review

    Posted 11-Apr-2019 09:55
    If the IND is placed on clinical hold then the IND is not active yet. See 21 CFR 312.40. I would expect that once the clinical hold is lifted, FDA will issue a Study May Proceed letter.  The Anniversary date would be the date that the IND became active which would be the date of the Study May Proceed letter.  Annual Reports would be due within 60 days of the Anniversary Date. Many times a sponsor will request permission to submit a DSUR instead of Annual Reports and to also change the anniversary date for submitting the DSUR to the Development International Birth Date (IBD) of the compound. This request must be submitted formally to the IND.

    ------------------------------
    Tom
    Sr. Director, Regulatory Affairs CMC
    Chicago
    ------------------------------

    Original Message


Related Content