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IND Submission (CMC- Related Topic)

  • 1.  IND Submission (CMC- Related Topic)

    Posted 22-Apr-2020 18:14
    In a typical IND submission, does a full versus partial stability report for drug product can lead to acceptance or postponement of IND? Can a company tell the FDA that it will submit the report later as the analysis is incomplete now ?

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    Shivam Mishra


    Québec QC
    Canada
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  • 2.  RE: IND Submission (CMC- Related Topic)

    Posted 23-Apr-2020 04:39
    It depends on what is missing. Having the report itself finalized is not as critical as whether the data you have available to submit provides stability for at least one month of accelerated and recommended storage conditions. If that analysis didn't include something like active ingredient or sterility for an injectable, then yes.

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


  • 3.  RE: IND Submission (CMC- Related Topic)

    This message was posted by a user wishing to remain anonymous
    Posted 20-Mar-2024 16:52
    This message was posted by a user wishing to remain anonymous

    Hello
    I know this thread is a few years old but I was wondering if it is possible to submit your initial IND without the CoA of your GMP batch? The guidance states that it is suggested to submit the CoA, and I interpret that as non mandatory. We have the intention of providing the CoA prior to the dosing of patients and can state this in the cover letter but want to ensure that this strategy does not lead to a clinical hold. Would appreciate to hear peoples experience of this.


    Original Message


  • 4.  RE: IND Submission (CMC- Related Topic)

    Posted 20-Mar-2024 18:17
    Hi Anon,

    CoA is optional if you provide the same results and specification information in Module 3.2.S.4 and 3.2.P.5 in your IND. FDA won't usually put you on clinical hold simply because you fail to proactively submit CoA.

    However I always provided it for the first batch in IND as an example.




    Original Message


  • 5.  RE: IND Submission (CMC- Related Topic)

    Posted 24-Mar-2024 17:27

    We generally do not submit CofAs to the IND. We put the batch analysis data in S.4.4/P.5.4.



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    Rachel Thornton
    Director
    Smyrna GA
    United States
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    Original Message


  • 6.  RE: IND Submission (CMC- Related Topic)

    Posted 25-Mar-2024 07:09

    As Rachel indicates, the data from the first clinical (GMP) batch needs to be in the IND, typically as a batch analysis table rather than providing the CoA itself. Typically, the batch analysis table would list side-by-side the data from the toxicology batch supporting the clinical trial and the clinical GMP batch to show that any impurities in the clinical batch have been qualified in the toxicology studies.  A commitment to supply the batch analysis data for the clinical GMP batch prior to dosing the first subject is typically not sufficient to meet the requirements for the IND and could lead to a clinical hold.  If this is your strategy, you may want to first get FDA agreement on this approach in a Pre-IND meeting.

    FDA also typically wants to see 1 month of stability data on a representative drug substance (and, perhaps, also drug product) batch in the initial IND submission with accelerated data.

    Good luck!



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    Mark A De Rosch, PhD, FRAPS
    Ruckersville, VA
    United States
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    Original Message


  • 7.  RE: IND Submission (CMC- Related Topic)

    Posted 23-Apr-2020 09:48
    Hi Shvam,

    It is typical to have the stability data for the CTM in the original IND submission as otherwise, depending on the Division, it is likely that they will not clear the IND during the 30-day review period.

    However, you can get agreement to delay the submission of the stability data to the IND after it has cleared if you have had a Pre-IND meeting & included this question as one of the topics so the Division knows that the stability data isn't going to be available in the original submission. If this has not been discussed in advance, you can go ahead & submit the IND with an explanation in the cover letter but you do run the risk of being put on Clinical Hold or being asked for the data during the review process. It will then depend on the reviewer if during the review you are unable to provide the data but commit to providing this data prior to the start of the study.

    Again, will depend on the Division but both tactics are options if you are constrained with the data not being available immediately.

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    Janaki Subramanyam RAC
    Executive Director, Regulatory Affairs
    Newton MA
    United States
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    Original Message


  • 8.  RE: IND Submission (CMC- Related Topic)

    Posted 23-Apr-2020 11:31
    Shivam,

    This really depends on the stage of development. Certainly the FDA recognizes that you will have limited stability data early on in development. Thus you can file in early stages with very limited data with promise to continue stability study and submit later at the request of the agency or in annual report. My assumption is that  when you are talking full vs partial stability report you are talking about missing  additional pull points.  However, for example, if you are talking about having  only a month worth of stability data with missing  test results, that will likely be unacceptable.

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    Robert Blanks RAC
    VP, Regulatory Affairs and Quality Assurance
    [Ardelyx]
    Auburndale MA
    United States
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    Original Message


  • 9.  RE: IND Submission (CMC- Related Topic)

    Posted 23-Apr-2020 11:42
    You should include adequate stability data to support the length of your clinical trial. Ideally this should be included in the original IND submission.  If you submit partial stability data in original IND, I would be sure to have the complete data available within the 30-day review period and anticipate FDA will request.  Otherwise I would expect you'd be at risk of being placed on clinical hold. Often it is acceptable to include only 1 month stability data in the original IND along with a commitment to amend the IND with additional data as it becomes available to support extension of the shelf-life of clinical supplies.

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    Tom
    Senior Director, Regulatory Affairs CMC
    Chicago
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    Original Message


  • 10.  RE: IND Submission (CMC- Related Topic)

    Posted 24-Apr-2020 00:09
    Hi Shivam,

    Can you please clarify what you mean by full vs partial stability report? Normally, you don't need to submit a stability report in IND.

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    Gene Zhu
    Independent Consultant
    Basking Ridge NJ
    USA
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    Original Message


  • 11.  RE: IND Submission (CMC- Related Topic)

    Posted 24-Apr-2020 01:22
    very good discussion! This is very interesting topic and there’s certainly a lot of ambiguity around having enough stability in your IND. I agree that it should be a phase appropriate approach. For earlier phases (FIH, phase 1b), limited stability data may be acceptable if supported with developmental stability from representative non-GMP batches. For later phase, FDA would expect to have more GMP stability studies with extended time points.

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    Deep Shah
    Regulatory Affairs CMC, Biologics

    Seattle WA
    United States
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    Original Message


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