Regulatory Open Forum

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  • 1.  IRB disagreement of NSR determination

    This message was posted by a user wishing to remain anonymous
    Posted 12-Dec-2023 15:00
    This message was posted by a user wishing to remain anonymous

    Hello RAPS colleagues,

    Questions regarding IRB disagreement of sponsor's NSR determination of an IVD.

    In the case of multiple sites where one IRB disagrees with sponsor's NSR determination, can sponsor continue to enroll patients in other sites which were active while waiting to receive FDA's determination? Or should the sponsor stop enrollment at all sites while waiting to receive FDA's determination? What happens to patients who are on treatment at those other sites? 

    The regulations under 21 CFR 812.66 states that if an IRB determines that an investigation involves a significant risk device, the IRB will notify the investigator and, where appropriate, the sponsor. The sponsor must notify FDA within 5 days under 21 CFR 812.150. Sponsor may not begin the investigation unless FDA action occurs under 21 CFR 812.30. 

    I interpreted the above regulations to apply to the entire study, not site-specific; therefore, the study must stop while awaiting FDA feedback. I believe this is a potential risk when approaching each IRB as opposed to seeking FDA determination up front. I would like to confirm the accuracy of (or correction of) my interpretation.  

    Thanks for any insights or experience anyone can share. 

  • 2.  RE: IRB disagreement of NSR determination

    Posted 13-Dec-2023 05:25


    We had something similar with a client in the past and they put the study on hold until they had the FDA decision.

    Good luck with your study.


    Olga Peycheva
    Regulatory and Study Start Up Specialist (Clinical trials)
    Solutions OP Ltd
    United Kingdom

  • 3.  RE: IRB disagreement of NSR determination

    Posted 13-Dec-2023 06:22

    Good day Anon,

    Similar to what Olga said, if you have an IRB disagreeing on the Significant Risk (SR) status of a device or IVD device, you can reach out to FDA for determination.  While the IRBs usually make the first determination, ultimately the FDA can make the decision.  As said, probably recommend putting things on hold until that is sorted because you do not want to get a bunch of patients enrolled and then end up having to submit an Investigational Device Exemption (IDE) through FDA.

    Richard Vincins ASQ-CQA, MTOPRA, RAC
    Vice President Global Regulatory Affairs

  • 4.  RE: IRB disagreement of NSR determination

    Posted 13-Dec-2023 06:38

    The notification to FDA would stop enrollment of the whole study. It is not clear if the IRB made the decision from the protocol alone or with a NSR justification crafted by the sponsor. It is a good idea to have a risk determination statement summarising the NSR logic following guidance for this purpose. For those subjects enrolled, any treatment must be paused until FDA makes a decision and and IDE is approved (if FDA determines SR). It is the obligation of the sponsor to determine risk (and document it for just this situation) and if there is any question, file to the FDA to avoid delays.

    Sarah Parsons RAC
    Director Regulatory Affairs, Diagnostics
    Northcoast Consulting