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preliminary reports of nonclinical studies in IND

  • 1.  preliminary reports of nonclinical studies in IND

    Posted 01-Oct-2012 08:52
    I'd like to hear the thoughts of others about the acceptability of preliminary reports of nonclinical studies in INDs.  If final reports are not yet available but the study results are in, would it be better to include the preliminary reports in Module 4 of the CTD and summarize the results in Module 2?  Or would it be better to include results in Module 2 only and then submit the final study reports to Module 4 later? 

    Has anyone had experience with this question?

    Many thanks,
    Kathy

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    Kathryn Wekselman
    Director, Regulatory and Scientific Affairs
    CTI Clinical Trial and Consulting Services
    Cincinnati OH
    United States
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  • 2.  RE:preliminary reports of nonclinical studies in IND

    Posted 02-Oct-2012 08:05
    Dear Kathryn,
    It is always good to send the FDA any nonclinical data you have, in my experience. However, you should send audited draft reports for any GLP safety evaluation studies. Please keep in mind that you will have a 180 day clock to complete and send the final reports once drafts are submitted. For non-GLP investigative reports (ADME or pharmacology), you can send summaries of the data if final reports are not available.
    Hope this helps,
    Al

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    Allen Pierce, MS, DABT
    Associate Director, Toxicology
    Molecular Insight Pharmaceuticals
    Acton MA
    United States
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  • 3.  RE:preliminary reports of nonclinical studies in IND

    Posted 02-Oct-2012 08:27
    Hi Kathy:

    Based on my experience, the FDA reviewers do need the reports containing data, they do not need to be final reports. Submission of data in M2 only is not acceptable and the IND may not be accepted for review. You can submit preliminary reports in the IND and be prepared to submit the final reports within 120 days or earlier if the FDA requests. When you submit the final reports, you need to add statement regarding any major changes between preliminary and final reports.

    Hope this helps.
    -------------------------------------------
    Kala Patel RAC
    Senior Director, Regulatory Affairs
    Akros Pharma Inc
    Princeton NJ
    United States
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    Original Message


  • 4.  RE:preliminary reports of nonclinical studies in IND

    Posted 03-Oct-2012 09:08
    Dear Kathy,

    If by "preliminary report" you mean a key results memo without data, then I would highly recommend waiting to submit until you have at least an audited draft study report containing data. This applies to those studies which may be important to address safety

    issues, or to assist in evaluation of toxicology data. If you submit an audited draft report in your IND, submit the final report once available to the IND (within 120 days) highlighting any differences, if any, between the audited and final reports.

    As per FDA guidance, for nonclinical pharmacology studies, a summary report, without individual animal records or individual study results, usually suffices.

    Good luck with your IND!

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    Antonella Lozito PharmD RAC
    Associate Director
    Sanofi
    Bridgewater NJ
    United States
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    Original Message


  • 5.  RE:preliminary reports of nonclinical studies in IND

    Posted 04-Oct-2012 04:28
    I am following this discussion and gettting mixed suggestions that are not consistent. Some say we should submit the final report within 60 days once you submit the audited draft report and some say within 120 days. What the guidance say? Please clarify.

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    Venkatesh Rao
    Regulatory Specialist II, Drug Regulatory Affairs
    Hyderabad
    India
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    Original Message


  • 6.  RE:preliminary reports of nonclinical studies in IND

    Posted 04-Oct-2012 09:49
    The applicable US regulations for an IND submission are silent on the following.

    1. whether the IND should be based on draft, unaudited reports; OR
    2. whether the IND should be based on final, fully quality assured reports.   

    Either type of submission (an integrated summary report based on #1 or #2) may be submitted for the IND to get going. 

    However, if the #1 is chosen, final, fully quality-assured reports should be available to the FDA within 120 days of the start of the human study.  

    Please note:  "As drug development proceeds, the sponsor is required to submit informational amendments, as appropriate, with additional information pertinent to safety."

    For example, sometimes, your final report needs to be revised to better meet the requirements or some additional studies are ongoing even after the IND submission...etc. 

    If that is the case, you can submit your final report as part of your annual reports within 60 days of the anniversary date that the IND went into effect.  

    In your IND annual report under "Summary Information," it asks for "Information obtained during the previous year's clinical and nonclinical investigations, including..."

    60 days or 120 days are fuels for you to use as part of your strategy.  

    --------------------------------------------------------
    Regulatory Doctor, Coach and Consultant
    www.GlobalComplianceSeminar.Com
    Riner VA
    United States
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  • 7.  RE:preliminary reports of nonclinical studies in IND

    Posted 05-Oct-2012 08:19
    This situation is actually clarified in the following FDA guidance:

    http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm078928.pdf

    In short, you must provide final audited reports within 120 days of FDA's receipt of your original IND.

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    Mark Ammann PharmD
    President
    Catalyst Regulatory Services, LLC
    Dexter MI
    United States
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    Original Message


  • 8.  RE:preliminary reports of nonclinical studies in IND

    Posted 02-Oct-2012 09:01
    Kathryn,
       If an other than final ("audited draft") form of a nonclinical study is submitted, the current guidance is that a final form must be submitted within 60 days. Because of the uncertainty in always being able to meet this requirement, the most common practice is to wait for the final reports (though as the proportion of sponsors/clients that are always in a time critical - "chihuahua on crack" - mode increases, adhering to this is more difficult). Either way, one cannot just present results in module 2 but not provide a report  in Module 4 until some later time. 

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    Shayne Cox Gad PhD, DABT, ATS
    Principal
    Gad Consulting Services
    Cary NC
    United States
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    Original Message


  • 9.  RE:preliminary reports of nonclinical studies in IND

    Posted 02-Oct-2012 09:17
    Hi! kathy,

    It is ok to submit the preliminary reports in the new IND per the conditions you described (study design/protocols and preliminary results are available). You can submit the final reports later on in the IND as an IND amendment. You should include as much information as available in the original IND, so if you have draft or preliminary reports in the IND with the note added to them that they are not final and that the final report will be submitted at a later time when it becomes available. I have done it multiple times with no issues from FDA review teams. If you have additional questions, please email me at mukeshk at amarexcro.com.

    Regards,

    Mukesh 

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    Mukesh Kumar RAC, PHD
    Senior Director, Regulatory Affairs
    Amarex Clinical Research
    Montgomery Village MD
    United States
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    Original Message


  • 10.  RE:preliminary reports of nonclinical studies in IND

    Posted 07-Oct-2012 09:45
    Dear All,

    The discussion on preliminary reports for nonclinical studies to the IND continues to demonstrate that "guidance" and the codified regulations are not specific and definitive on these types of discussions.  It also appears from the discussion that there are many "experiences" and I would argue that it depends on your review Division.  My experience has been that for "pivotal" toxicology studies for the Divisions I have worked with have agreed during the pre-IND meeting (which your IND strategy tox strategy should be discussed) that draft reports (not final audited reports) are acceptable for the IND submission but within 120 days as with the 120 day clinical safety update final reports (GLP audited) would be needed. If you have not had this discussion during your pre-IND meeting, I encourage you to discuss your strategy with the project manager or with the pharm/tox reviewers if you know who it is by the time you have your pre-IND meeting.

    Key to this discussion is not what is prescriptive in a guidance which is not regulation, is to understand what is "current" practice and what makes sense for your project.  Also key is that by the time the final report is available, that the conclusions provided from the draft report are not changed and that a worse tox profile is identified due to errors in data and calculations.  It also depends on your companies tolerance for risk. 

    From my perspective, the lowest risk scenario is to plan for the final reports (again pivotal toxicology studies) to be included in your IND; have a discussion with FDA during your pre-IND meeting on submitting draft reports and understand the business goal and objective in the timing of filing an IND.  All of this information should help drive your strategy.

    One last consideration is the novelty of your investigational agent, small molecule or biologic, novel or "me too" and planned indication. If you have any hints from earlier non-GLP studies such as ADME or PK and preliminary tox that indicates any signals of concern, plan to submit final reports to minimize any risk of clinical hold based on safety concerns.

    In the end, these discussions are not simple or based strictly on guidance or regulation but should encompass broader considerations that are strategic.

    All the best,

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    Darlene Rosario
    VP Regulatory Affairs and Quality
    Biothera
    3388 Mike Collins Dr.
    Eagan, MN
    United States
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