Regulatory Open Forum

 View Only
Expand all | Collapse all

IND- CSR Submission

  • 1.  IND- CSR Submission

    This message was posted by a user wishing to remain anonymous
    Posted 03-Nov-2021 11:17
    This message was posted by a user wishing to remain anonymous

    Hi All,

    For a clinical study done for an IND, is there a timeline within which the CSR must be submitted for the agency. 

    thanks!


  • 2.  RE: IND- CSR Submission

    This message was posted by a user wishing to remain anonymous
    Posted 03-Nov-2021 16:57
    This message was posted by a user wishing to remain anonymous

    one year from the completion of study


  • 3.  RE: IND- CSR Submission

    Posted 04-Nov-2021 08:09
    I am not aware of a regulatory requirement to submit a CSR to the IND within any specific timeline. Obviously, information from a completed clinical study would be included in the IND Annual Report and the Investigator Brochure. Further, it may be beneficial to submit a CSR to provide the full database for Agency review, particularly if there are critical safety issues. However, in my experience it is not unusual not to submit a CSR to the Agency until NDA submission.

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



  • 4.  RE: IND- CSR Submission

    This message was posted by a user wishing to remain anonymous
    Posted 04-Nov-2021 16:55
    This message was posted by a user wishing to remain anonymous

    My advise is for you to submit within one year of completion date. If one requires to comply with the FDAAA 801 and the Final Rule (see below FAA), I'd suggest you do the same to the FDA review division. 
    Old school it wasn't a practice to submit CSR to the IND, but the new school of thought after the FDAAA 801 regulations, 42 CFR 11, it's better you submit it.

    https://clinicaltrials.gov/ct2/manage-recs/faq#42CFRPart11


    • "If the ACT studied a drug, biological, or device product that was approved, licensed, or cleared by FDA before the ACT's primary completion date, the responsible party generally must submit the results information specified in section 402(j)(3)(C) and section 402(j)(3)(I) of the Public Health Service (PHS) Act no later than 1 year after the study's primary completion date; however, results information submission for these ACTs may be delayed under certain conditions as specified in section 402(j)(3)(E)(v) (seeking approval, licensing, or clearance of a new use for the drug, biological, or device product) and section 402(j)(3)(E)(vi) (requesting an extension for good cause) of the PHS Act."



  • 5.  RE: IND- CSR Submission

    Posted 05-Nov-2021 08:45
    Hi Anon - old school or new school, I don't think you can use the requirement to submit results to clinicaltrials.gov as a basis for recommending submission of a CSR to FDA within one year after study completion. I usually recommend delaying submission of results for ACTs that are intended to be submitted for a new use for a drug, biological, or device product for competitive reasons. So, connecting the submission of the CSR to the IND would have nothing to do with a requirement to submit results to clinicaltrials.gov.

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



  • 6.  RE: IND- CSR Submission

    This message was posted by a user wishing to remain anonymous
    Posted 05-Nov-2021 12:46
    This message was posted by a user wishing to remain anonymous

    Since 2017, lot of companies both big pharma and the small companies are submitting the CSR's to the FDA, if not within one year very close to that! They are being transparent and don't want the FDA blindsided.


  • 7.  RE: IND- CSR Submission

    Posted 05-Nov-2021 13:26
    I do not understand why FDA would consider they have been blindsided when the efficacy and safety results from the study are included in the IND Annual Report and the updated Investigator Brochure.

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



  • 8.  RE: IND- CSR Submission

    Posted 06-Nov-2021 07:07
    Hi Glen and Anon,

    I agree, the clinicaltrials.gov extension is different. I'm also not aware of any requirement or timeframe to submit a CSR to an IND.  They are separate, but this could be used to your advantage.

    I was previously a part of a submission team that requested the extension for clinicaltrial.gov results requirements (for results reporting) - under criteria in section 402(j)(3)(E)(v) - seeking approval, licensing. It was granted, and we held the CSR to include in a planned NDA submission.

    Keep in mind that any information submitted to an application may be requested by a third party under the FOIA. So this approach could be to your advantage from a strategic standpoint.

    ------------------------------
    Joe Benner RAC
    ------------------------------



  • 9.  RE: IND- CSR Submission

    Posted 08-Nov-2021 11:38
    Both arguments appear sound! However, I don't think that submitting clinical trial summary results in an IND annual report or summarizing in an IB is equivalent to a formal CSR of a clinical study! Politically or from the public perspective transparency of trials results have become a hot topic recently so I agree with the above Anon's comment that most of big pharma submitting CSR's to the IND as well as complying with the FDAAA 801. 

    ------------------------------
    GRSAOnline
    ------------------------------



  • 10.  RE: IND- CSR Submission

    This message was posted by a user wishing to remain anonymous
    Posted 10-Nov-2021 22:53
    This message was posted by a user wishing to remain anonymous

    Hello, 

    I agree that there is not a right or wrong answer, but the transparency factor is important to consider, and giving FDA full data in real time is a step toward that.  Another thing is that documents can get "lost" when products are sold to another company; one of the things that is seldom lost is a IND, so if the report has been submitted to the IND, it should be easily retrievable. 

    FOIA is generally not applicable to an IND, only to NDAs or BLAs that have been approved, so I don't think that should be an overriding concern in submitting a CSR to the IND.  In addition, since Applicable Clinical Trials have to have results posted on clinicaltrials.gov (whether delayed for NDA approval or not, this has to be done at some point even if an NDA is never approved), and these results must be accompanied by the most recent versions of the protocol and the SAP, there is probably little left in the CSR that is proprietary.


  • 11.  RE: IND- CSR Submission

    This message was posted by a user wishing to remain anonymous
    Posted 11-Nov-2021 14:36
    This message was posted by a user wishing to remain anonymous

    Perfect example of an old versus new school of regulatory perspectives!!! Very good point when a company is sold to another,  during due diligence if the acquiring company finds out that the CSR for a clinical study (either a mere pk/pd or preliminary exploratory efficacy etc) was not submitted that could cause doubts on the findings of these studies summarized only in the annual reports or press releases etc.. and in my experience we walked away from acquiring a company unless the CSR (s) was/were submitted to the IND.
    In the current drug/biologic development/business perspective, a true senior level regulatory strategist has to look in every angle, not just focus on regulations, in providing advise to the management.


  • 12.  RE: IND- CSR Submission

    Posted 11-Nov-2021 15:01
    From my experience, old school regulatory makes hard rules that have to be followed whether it is in the regulations or not. New school regulatory says that we should follow the regulation to the letter when it says you "shall" do something and use common sense in all other cases. There is no regulation that says you "shall" submit a CSR within one year of clinical study completion (which was the original question addressed in this thread).

    I cannot imagine walking away from a potential acquisition on the sole basis that a company did not submit a CSR to a regulatory authority because not doing so cast doubts on the integrity of the data. Due diligence is based on reviewing the reports themselves and determining the integrity of the data on first hand, and not whether it had been submitted to the IND. Unless the FDA has a reason to review a CSR to make a safety decision during development, one cannot be certain that they have made a judgement about the integrity of the data. And, even then, they could be wrong.

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