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  • 1.  Risk Management & Off Label Use

    This message was posted by a user wishing to remain anonymous
    Posted 27-Mar-2020 08:50
    This message was posted by a user wishing to remain anonymous

    My colleagues and I are discussing the 14971 part about foreseeable misuse.

    Some people think that if we know about off-label use, that is foreseeable misuse and we need to include it.

    Some people think that including it means supporting it, because the risk management would look at any issues. If FDA finds out, they could take action against the company.

    I'd like to hear how others handle this issue.



  • 2.  RE: Risk Management & Off Label Use

    Posted 27-Mar-2020 09:29
    I look at this as the key term being "foreseeable" in this issue.  If you can reasonably expect that a user would handle or use the product in the manner then that is foreseeable.  If you know that the product is being used in an off-label manner then I think you have a responsibility to include it, review it, and potentially mitigate against it.  But this is just my take/opinion on this point.

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    Victor Mencarelli
    Global Director Regulatory Affairs
    MelvilleNY
    United States
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  • 3.  RE: Risk Management & Off Label Use

    Posted 27-Mar-2020 16:00
    14971:2019 added a definition for reasonably foreseeable misuse, "use of a product or system in a way not intended by the manufacturer, but which can result from readily predictable human behavior". This needs to consider all types of users and can be intentional or unintentional. I think there are several things at play in the question.

    Here is a link to an FDA guidance on responding to unsolicited requests for off label information https://www.fda.gov/media/82660/download FDA expects manufacturers to field these requests with truthful, balanced, nonmisleading and non-promotional information. This includes communicating the risks involved with the off-label use, implying that the manufacturer has considered it.  

    Manufacturer implementation of ISO 14971 is quite variable. Manufacturers I work with require a cross functional team to be involved in the risk management process to ensure things are not missed. Particularly important is the medical affairs that usually provide the hazard analysis on the front end of the process and sign off on the overall results on the back end, at a minimum. One of the inputs to the process is post market surveillance, where off label use may surface. It seems reasonable to me that a risk management team would consider the off label use and assess the risk per usual and decide which, if any, additional risk mitigations need to be considered. Ignoring post market information will get a manufacturer in trouble, for sure.

    Hope it helps.




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    Adam Atherton
    Farragut TN
    United States
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  • 4.  RE: Risk Management & Off Label Use

    Posted 28-Mar-2020 08:48

    Adam is right on target with his response. It is important that when a company learns about an off-label use that they use the process required in Clause 10 to identify the risks associated with this use and add any risk controls required to reduce these risks.  It is very important that the company not ignore any information they learn about their product performance and safety.

    Another possibility here is when a manufacturer learns about an off-label use is a potential opportunity to expand the indications for the product. It may require some clinical trials and other regulatory activities such as a new submission to accomplish this. But with the product on the market for its original indications the company would have an income stream to perform the necessary activities to expand the indications. 


    I also want to commend Adam in his approach outlined in the last paragraph to operate the risk management process. They are looking at the process not as a checkbox activity like some, but a true risk management process to improve safety in medical devices. 



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    Edwin Bills MEd, CQA, RAC, BSc, CQE, ASQ
    Principal Consultant
    Overland Park KS
    United States
    elb@edwinbillsconsultant.com
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