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  • 1.  IND annual report

    This message was posted by a user wishing to remain anonymous
    Posted 28-Nov-2022 09:03
    This message was posted by a user wishing to remain anonymous

    Hello RAPS Community,

    I have a couple of questions about submitting an annual report for IND. Here is some basic information. 

    1) review division: CDER 2) clinical trial has not started (no patient has enrolled) 3) No new non-clinical studies 

    Questions:

    1) We have not enrolled any patients and did not conduct any new non-clinical studies, and have no manufacturing or microbiological or labeling changes; I assume we do not need to submit the following documents.

    • 1.13.1 Summary of Nonclinical Studies
    • 1.13.2 Summary of Clinical Pharmacology Information
    • 1.13.3 Summary of Safety Information
    • 1.13.4 Summary of Labeling Changes
    • 1.13.5 Summary of Manufacturing Changes
    • 1.13.6 Summary of Microbiological Changes

    Am I right?

    2) We have updated stability data. We plan to (should we?) submit updated M 3.2.P.8.1, M 3.2.P.8.2, M 3.2.P.8.3, M 3.2.S.7.1, M 3.2.S.7.2, and M 3.2.S.7.3. Can we mention in the cover letter that we are submitting these updated documents? Or do we need to write something in the M 1.13.7 (Summary of Other Significant New information)?

    Thank you!



  • 2.  RE: IND annual report

    This message was posted by a user wishing to remain anonymous
    Posted 28-Nov-2022 17:04
    This message was posted by a user wishing to remain anonymous

    FYI-For CMC changes for INDs, you need to submit as they occur and submit them as Amendments (i.e. before using in trial with the new change) and don't wait until annual report! Updated stability data or any minor updates to the sections already submitted in the original IND are ok to be submitted in the Annual Report!

    Any significant CMC change need to be submitted as they occur NOT in the Annual Report!

    If trial has not started, then you submit the AR with a statement under each section that nothing new happened during the reporting period since the Original IND was okayed!
    Original Message


  • 3.  RE: IND annual report

    Posted 29-Nov-2022 12:02
    All of this information is correct. You may also consider submitting a single Development Safety Update Report (DSUR) in lieu of each 1.13.X summary document (see https://www.fda.gov/files/drugs/published/E2F-Development-Safety-Update-Report.pdf for more information on the DSUR). It's less work from a publishing standpoint and, since you have no information to share, may be easier to manage. There's a comparison of the DSUR Guidelines to Annual Report CFR Requirements listed here: https://www.tech-res.com/TRIbune/Fall_2012/Comparison-of-DSUR-Guidelines-to-AR-CFR-Requirements.pdf

    However, if you choose to submit the DSUR format, note that you will not revert back to using the annual report sections 1.13.X - you'll move forward using the DSUR format entirely. Also consider if your product will have multiple formulations, etc., in the future, which would affect how easy the DSUR may be to develop in future reporting periods.

    ------------------------------
    Ashley Butler
    Sr. Manager, Regulatory Operations
    Cambridge MA
    United States
    ------------------------------

    Original Message


  • 4.  RE: IND annual report

    Posted 29-Nov-2022 13:54
    The ANON reply was correct, CMC is required to be submitted outside the annual report.  Please see this link:
    IND Application Reporting: Annual Reports | FDA

    Here is the required info in the IND annual report with a 1571 cover page from that link: (note how NONE of the info below requires FDA response or timely review like the CMC changes might - the goal for the IND Annual report is to not submit ACTIONABLE items in the IND, ALL ACTIONABLE items have separate reporting requirements). This is meant to be a simple summary of study changes in the past year to be on file at the FDA within 60 days of the IND anniversary date.

    Individual study information 

    A brief summary of the status of each study in progress and each study completed during the previous year. The summary is expected to include the following information for each study: 

    1. The title of the study (with any appropriate study identifiers such as protocol number), its purpose, a brief statement identifying the patient population, and a statement as to whether the study is completed.

    2. The total number of subjects initially planned for inclusion in the study; the number entered into the study to date, tabulated by age group, gender, and race; the number of participants who completed the study; and the number who dropped out of the study for any reason.

    3. A brief description of any available study results. 

    Summary information  

    Information obtained during the previous year's clinical and nonclinical investigations conducted under the IND application, including: 

    1. A narrative or tabular summary showing the most frequent and most serious adverse experiences by body system.

    2. A summary of all IND safety reports submitted during the past year.

    3. A list of subjects who died during participation in the investigation, with the cause of death for each subject.

    4. A list of subjects who dropped out during the course of the investigation in association with any adverse experience, whether or not thought to be drug related.

    5. A brief description of what, if anything, was obtained that is pertinent to an understanding of the drug's actions, including, for example, information about dose response, bioavailability, or relevant information from controlled trials.

    6. A list of the preclinical studies (including animal studies) completed or in progress during the past year and a summary of the major preclinical findings.

    7. A summary of any significant manufacturing or microbiological changes made during the past year. 
    Update to the General Investigational Plan   A description of the general investigational plan for the coming year to replace that submitted 1 year earlier.  

    Update to Investigator's Brochure  

    		 If the Investigator's Brochure has been revised, a description of the revision and a copy of the new brochure. 

    Significant protocol updates 

    A description of any significant Phase 1 protocol modifications made during the previous year and not previously reported to the IND in a protocol amendment. 

    Update on foreign marketing developments 

    A brief summary of significant foreign marketing developments with the drug during the past year, such as approval of marketing in any country or withdrawal or suspension from marketing in any country. 

    A log of outstanding business 

    If desired by the sponsor, a log of any outstanding business with FDA with respect to the IND application for which the sponsor requests or expects a reply, comment, or meeting. 


    ------------------------------
    Joy Frestedt PHD, CPI, RAC, FRAPS, FACRP
    President and CEO
    Frestedt Incorporated (www.frestedt.com)
    Saint Louis Park MN
    United States
    612-219-9982
    jf@frestedt.com
    ------------------------------

    Original Message


  • 5.  RE: IND annual report

    This message was posted by a user wishing to remain anonymous
    Posted 29-Nov-2022 15:23
    This message was posted by a user wishing to remain anonymous

    Regardless of whether your clinical trial has any participants, IF it's been submitted to your IND it may be a good idea include it under on-going studied but mention that as of the data lock point no patients have been enrolled.
    Updated and new manufacturing data should be submitted to your IND as soon as they are ready as an Information Amendment and then summarized in the summary of manufacturing changes section in your Annual Report.  If the due date of your annual report is close you could opt to submit the updated sections in Module 3 as an information amendment at the same time as your annual report this would be in addition to the updated section 1.13.5 in the AR.  You would select AR and IA:chem/micro in your 1571.  Essentially you'll be killing 2 birds with one stone.  It will catch up your application and you can maintain better moving forward.
    I've seen annual reports that excluded sections BUT in a DSUR I've seen a statement saying something like No new labeling changes occurred during the reporting period, etc.  You could do the same in an annual report.
    As always, consult the CFR and guidances for the best advice.
    Original Message


  • 6.  RE: IND annual report

    Posted 05-Dec-2022 11:17
    I've always included stability updates under 1.13.5. The title may be "Manufacturing Changes" but I've always seen all CMC changes included there. So we include a summary of the change in 1.13.5 (e.g., The 12M stability timepoint is now available and the data are provided in Section 3.2.P.8.3) and then submit the relevant updated Module 3 sections.

    I don't see why you would need to submit S.7.2 and P.8.2 - has something changed there?

    ------------------------------
    Rachel Thornton
    Associate Director
    Smyrna GA
    United States
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    Original Message


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