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  • 1.  Use of multiple predicates to support substantial equivalence

    Posted 05-Sep-2017 23:58

    Dear Regulatory Colleagues,

    I would like to solicit input on the use of multiple predicates to support substantial equivalence.  According to FDA Guidance document "The 510(k) Program: Evaluating SE in Premarket Notifications [510(k)] issued on July 28, 2014, we are allowed to use multiple predicates.  Using Example 5 from the Guidance, in which the subject device is a urinary catheter with a thermometer, and the primary predicate is a legally marketed catheter (without the thermometer component).  As one goes through the SE Determination Flowchart, Decision Points 3 pertains to the technological characteristics of the subject and predicate device.  The Guidance states that the FDA must be able to address Decision Points 1 through 4 in the Flowchart using one predicate device identified by the manufacturer, but how does one compare the subject device to the primary predicate when it doesn't have the temperature component?  

    Thanks and look forward to your input.


    Regards,



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    Dawn Chang
    San Jose, CA
    United States
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  • 2.  RE: Use of multiple predicates to support substantial equivalence

    Posted 06-Sep-2017 00:42
    Dawn,

    I was finalizing my 510(k) workshop tomorrow.

    At decision point 3, it asks "Do the devices have the same technological characteristics?"

    For your case, your subject device has different technological characteristics and thus, you should go to the next Decision 4, which asks "Do the different technological characteristics of the devices raise different questions of safety and effectiveness?"

    If Yes at Decision Point 4, NSE.  If NO, FDA will review the proposed scientific methods for evaluating new/different characteristics' effects on safety and effectiveness."

    In this process, you should rely on your methods of tests and risk management to mitigate and control potential risks posed (e.g., by not having temperature component).  You should provide scientifically sound and clinically meaningful justification and then state your subject device doesn't raise different questions of safety and effectiveness. 

    Thank you.

    s/ David
    ______________________________________________
    Dr. David Lim, Ph.D., RAC, ASQ-CQA 
    REGULATORY DOCTOR
    Phone (Toll-Free): 1-(800) 321-8567

    NOTICE: This communication (including any attachments) may contain privileged or confidential information intended for a specific individual and purpose, and is protected by law. If you are not the intended recipient, you should delete this communication and/or shred the materials and any attachments and are hereby notified that any disclosure, copying or distribution of this communication, or the taking of any action based on it, is strictly prohibited.





    Original Message


  • 3.  RE: Use of multiple predicates to support substantial equivalence

    Posted 06-Sep-2017 11:02
    ​Hi Dawn,

    I agree with David - it is probably much easier to review the impact on safety and effectiveness of the feature rather than use an additional predicate device to do so.

    It is my understanding that FDA used to be receptive to the use of multiple or split predicate devices, but that they aren't fond of this approach any more.  Here is an article that I found on the subject: http://www.fiercebiotech.com/medical-devices/fda-final-guidance-modifies-510-k-rules-discourages-use-multiple-predicate-devices.

    I have heard from FDA reviewers that if you are going to use 2+ predicate devices, you need to compare every feature for all identified predicate devices - you cannot use one device to show equivalence of a single feature - so potentially you will have a device which has only 1 commonality with your device - and you will have many more differences that you will need to defend.

    Hope this helps,
    Liz

    ------------------------------
    Elizabeth Goldstein RAC
    Regulatory Affairs Project Manager
    United States
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    Original Message


  • 4.  RE: Use of multiple predicates to support substantial equivalence

    Posted 06-Sep-2017 12:22
    Edited by Daniel Petersen, RAC 07-Sep-2017 10:15
    So this is always a hot topic it would seem.  I have recently submitted a few 510(k)s with multiple predicates and the only critical component was addressing one as a primary predicate and then the others as secondary/supplemental predicates.  The primary predicate should have the same indications and product code(s) that you are applying for.  The secondary predicates can then be used to claim equivalency to specific features or technology.  Mind you they should be as similar as possible to avoid additional rounds of questioning.

    This is a rough example, but I had an orthopedic implant that was identical to the predicate in every way except for the porous coating.  I used a secondary predicate of a similar device that utilized the new coating technology and it cleared without question.  If you can support your claim of substantial equivalency, then you shouldn't have any issue with 2+ predicates.

    That being said I do agree with the previous commenter in that the FDA is trying to move away from that and discourage it for the most part, but until they release a new guidance they are still bound by it.

    Thanks for the question!

    EDIT:  I wanted to add this information from the same guidance referred to further explain my answer:


    "When demonstrating substantial equivalence in a 510(k) submission, manufacturers sometimes direct attention to similar situations FDA has encountered in the past. If a manufacturer successfully navigates through Decision Point 4 on the Flowchart using a single predicate device, other legally marketed devices, which FDA calls “reference devices,” may be used to support scientific methodology or standard reference values at Decision Point 5a. 

     

    It is important to note that a reference device is not considered a predicate device and it cannot be used to address Decision Points 1 – 4 on the Flowchart. Additionally, the applicability of a reference device will need to be reviewed by FDA for its appropriateness. If a selected reference device is used in an anatomical location or for a physiological purpose that is considerably different than that of the new device, its utility as a reference device may be limited. 

     

    If a manufacturer intends to use a reference device, the manufacturer should provide a scientific rationale that justifies its use. 

    I followed the “reference device example 1” exactly in my latest submission.  I did not use multiple "predicates" as i may have eluded to previously.  I used one predicate and two "reference devices".  Hope this helps!


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    Dan Petersen
    Regulatory Affairs Specialist
    Draper UT
    United States
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    Original Message


  • 5.  RE: Use of multiple predicates to support substantial equivalence

    Posted 07-Sep-2017 03:53
    We've had a similar experience to Daniel getting multiple predicate devices cleared.  It takes a well-constructed argument and a search for other multiple predicate clearances as well as using examples from FDAs own guidance as Dawn had done.  I also liked the idea of justifying the change as others have suggested with risk mitigation.  As a general rule FDA does not like multiple predicates but that is often the way predicate families advance innovation.

    Mark DuVal, J.D., FRAPS
    DuVal & Associates, P.A.


    Sent from my Verizon, Samsung Galaxy smartphone



    Original Message


  • 6.  RE: Use of multiple predicates to support substantial equivalence

    Posted 06-Sep-2017 14:02
    Hi Dawn, 

    I agree with the previous responses to this. Additionally, to compare the subject device with the primary predicate you create a table which compares the technological characteristics of each and <g class="gr_ gr_217 gr-alert gr_gramm gr_inline_cards gr_run_anim Grammar multiReplace" id="217" data-gr-id="217">identify</g> if the two are comparable. For the characteristics that are not identical, then you need to create a section where you explain in detail the differences and be sure to provide a rationale as to why the safety of effectiveness is not impacted. Given a thermometer is a more passive component, it's unlikely that this would lead to new safety concerns but you will need to perform a thorough risk assessment to justify this.

    ------------------------------
    Rory Carrillo
    RAC Medical, LLC
    San Francisco CA
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    Original Message


  • 7.  RE: Use of multiple predicates to support substantial equivalence

    Posted 06-Sep-2017 14:16
    Example 5 resolves the temperature measurement capability from the urinary catheter in the the feature which measures temperature. This addition does not impact the intended use or performance of the catheter. 

    Earlier in the guidance the agency notes that features may be combined when the same intended use is preserved, seeking to market a device with more than one intended use, or when seeking more than one indication for use under the same intended use.

    I believe the key question is resolution; can the functions be resolved? The agency is clear on its objection to split-predicates and the examples clearly differentiate a multiple predicate from a split-predicate.

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    Timothy Kline, Ph.D., RAC
    Associate Manager, Regulatory Affairs
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    Original Message


  • 8.  RE: Use of multiple predicates to support substantial equivalence

    Posted 07-Sep-2017 00:15
    Thank you so much for everyone's helpful and valuable input.  Really appreciate it.
    Dawn

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    Dawn Chang
    San Jose, CA
    United States
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    Original Message


  • 9.  RE: Use of multiple predicates to support substantial equivalence

    Posted 08-Sep-2017 09:45
    Great discussion folks!
    One lesson I learned from some of my reviewers is that they are picky about the terminology and adhering to 2014 guidance sites in the original post i.e. primary predicate is THE predicate, secondary predicate is a 'reference' device.
    The reference device can be used to explain the safety of a technology while the predicate has to have one-to-one mapping with the subject device. So to continue the explanation with the example provided, here is a rough sketch IMHO:
    Predicate = standard urology catheter
    - illustrate identical indications
    - illustrate identical intended use
    - take credit for equivalent material for biocomp
    - take credit (where possible) for sterilization and packaging methodology

    Reference = another electronic thermometer that has mucus layer contact and similar contact duration
    Assumption: you are measuring temperature via an electronic means.
    - illustrate safety profile of similar technology used in a 'similar' body region. I say similar because you might be able to show that the device is used in another body part but the contact might be limited to mucus layer.
    - be explicit about calling this 'reference device' and your intent is to illustrate the safety of the extra technology you have in your device.
    - illustrate that this tech does not alter intended use
    - illustrate that this tech does not alter remaining function of the device i.e. the function of your device as a catheter.

    Hope this helps.
    Thas

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    Thas Yuwaraj
    Synaptive Medical
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    Original Message


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