Regulatory Open Forum

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  • 1.  De Novo Submission

    Posted 31-Aug-2020 16:46

    For De Novo submissions, does anyone know what the expectation is as far as determination for eligibility beyond that which is contained in the FDA guidance? What is the best way to make the argument that your device does not fall into any existing classification? How many searches for predicates do you have demonstrate? Are they looking at a comprehensive report of everything? How do you determine what is sufficient? The guidance states:

    "The De Novo request includes a classification summary that explains why the subject device is eligible for De Novo classification,
    including: The searches used to establish that no legally marketed device of the same type exists. Based on the searches, a list of the classification regulations, PMAs, 510(k)s, and/or product codes regarding devices that are potentially similar to the subject device. A rationale explaining how the subject device is different from the devices covered by the classification regulations, PMAs, 510(k)s, and/or product codes identified in the searches.



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    Jenna Horsley RAC
    Senior Regulatory Affairs Manager
    Cambridge MA
    United States
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  • 2.  RE: De Novo Submission

    Posted 01-Sep-2020 04:36
    Hello Jenna,

    In basic terms you have to show "due diligence" of ensuring the subject device going through the De Novo process is indeed eligible for the process, meaning the 510(k) pathway or PMA pathway are not appropriate.  In most cases, the 510(k) pathway is easy to determine because a Product Code and Regulation Number is needed and then a predicate device in order to establish substantial equivalence.  The databases FDA has available makes this a fairly administrative process, such as the 510(k) database, of course depending on the device type and what is being reviewed.  Probably the more challenging is showing the device is eligible for De Novo being a low to moderate risk device and not automatically being classified as Class III based on risk of the device.  There are guidance documents FDA has published to help with determining risk of a device and whether it would be eligible for the De Novo pathway.  To answer your questions you have to "build a regulatory pathway" for your device and how it would be regulated.  The main purpose of the De Novo submission is stating to FDA why your device would be eligible with all of the supporting information.

    It can be quite involved probably more than this forum post, but you would review the Product Codes, Regulation Numbers to see if there is anything close.  This all centres around your product's indications for use statement.  There may be some Product Codes or regulation description that might be close to the indications for use, so would need to describe the similarities or more the differences why it would be eligible under Do Novo ... and not fall into the PMA realm.  Then would review any potential predicate devices based on the regulation and Product Code.  You question about how do determine what is sufficient - that is a hard question to answer from a regulatory perspective.  The advice I would give is not so much about showing whether there is a regulatory pathway through 510(k) as this is fairly straight forward.  What is more important is creating the benefit-risk analysis of the device showing you would not automatically fall in a PMA pathway.  Also utilising expert help in developing regulatory pathways can be used to ensure all the important points are addressed and presenting to FDA a well thought through pathway leading to a potential De Novo submission.

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    Richard Vincins RAC
    Vice President Global Regulatory Affairs
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  • 3.  RE: De Novo Submission

    This message was posted by a user wishing to remain anonymous
    Posted 01-Sep-2020 08:36
    This message was posted by a user wishing to remain anonymous

    I've assumed this requirements means you have to absolutely, positively, show that there is no other product code for a similar type of device.
     
    Similar to what Richard raised, the 510(k) searches are easier. The harder ones are the Class 1 or Class 2 510(k) exempt codes. So one idea is to also search FDA's establishment and registration database for those products. What I did is download the raw files from FDA, connect them together through a database program (or Excel's Power Query), and then searched for every product under a couple 510(k) exempt product codes too. That way I was absolutely sure there was nothing similar.
     
    One thing to keep in mind is that you can submit a 513(g) beforehand to have FDA confirm the de novo pathway. Then, you just need a search that covers the time period in between the 513(g) conclusion and the submission of your de novo.



  • 4.  RE: De Novo Submission

    Posted 01-Sep-2020 09:30
    Hi Jenna - Similar to what Richard said, you need to demonstrate due diligence in making sure there isn't a viable predicate device (510(k)) or a similar device already approved through a PMA. In essence, you want to present a coherent argument to explain that your device is fundamentally different from all other devices currently classified and regulated by FDA, in terms of intended use and/or fundamental technology.

    Submitters take many different approaches to this depending on the type of product. For some products, it is so unique that an exhaustive search probably isn't necessary; you can likely just focus your search on a few regulations/product codes. For others, it may be similar enough to other existing devices that you'l need to be more nuanced and widen your search.

    The safest and most exhaustive way to determine eligibility on your own, in my opinion, is as follows (this is exactly what the FDA review team does when they receive an original De Novo):
    1. Identify search terms that you believe would most likely generate products possibly similar to your device. These are usually based on words stemming from the intended/indications for use and fundamental technological characteristics.
    2. Use these search terms in each of the public databases (eCFR, product codes, 510(k), PMA, De Novo)
    3. For each search result, explain why your device is fundamentally different (e.g., new intended use, new indication that represents a new intended use, different technology that raises different questions of safety/effectiveness, different/new risks to health)
    4. Your device must be different from everything you find in your search.

    The absolute safest way is to ask FDA! While you can submit a 513(g), I can't recommend enough the use of the pre-submission process to ask the FDA team directly about regulatory pathway, based on your research. If the review team believes your product is eligible for De Novo classification, then you're golden. Of course, the pre-sub process is also a good way to understand FDA's expectations for data and evidence to support De Novo classification of your new device type.

    Hope this helps,

    Sergio

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    Sergio de del Castillo
    De Novo Program Lead
    Silver Spring MD
    United States
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  • 5.  RE: De Novo Submission

    Posted 01-Sep-2020 11:25

    Thank you Sergio and Richard for your helpful answers. You have provided a great summary of how to approach a De Novo submission process. I really appreciate your insights into the exhaustive review that FDA performs when they review an original De Novo.

    Regards,

    Chris



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    Christopher Phillips, MSHS, RAC, CBA
    Regulatory Affairs Senior Manager
    Cottonwood Heights UT
    United States
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  • 6.  RE: De Novo Submission

    This message was posted by a user wishing to remain anonymous
    Posted 01-Sep-2020 16:54
    This message was posted by a user wishing to remain anonymous

    I too have hard the traditional advice that it is better to go for a Pre-Sub rather than a 513(g). I do want to share my experience that I posted previously.

    We went to FDA on a PreSub and one of our questions was about the choice of predicate device. In the preliminary feedback, they expressed a concern that our device did not have the technology that was in the name of the product code, and therefore could raise new questions of safety and efficacy. At the teleconference, while they entertained a little bit of discussion, they basically told us we needed to submit a 513(g). That was in May. We submitted our version of the meeting minutes within 15 says, received a question from the lead reviewer at day 30 asking where the meeting minutes were, and since then, have only been told they are working on the meeting minutes. Frustrated, we submitted a 513(g) a few days ago.


  • 7.  RE: De Novo Submission

    Posted 02-Sep-2020 10:03
    I would not be inclined to base future regulatory strategy on anything FDA is doing right now.  To me this sounds like it simply kicked the can down the road, probably due to inadequate resources to deal with everything it has on its plate.

    If you wanted to be bold, I would say don't submit a 513(g) just because FDA says so.  Like a pre-sub, a 513(g) isn't binding, which I think is the point.  FDA is trying to avert having to make a binding decision, which it will have to do it you submit a 510(k) or a De novo.  The bold move would be to submit whichever one of the two you think is appropriate.  If you are trying to avoid a De novo, you may be working on a textbook example of a case in which the time and money spent pursuing a 510(k) over a De novo was more than if you had just one forward with the De novo.

    On the other hand, if you are doing all this primarily because of investors, that is probably a textbook example of something else. :)

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    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Mebane, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
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  • 8.  RE: De Novo Submission

    Posted 02-Sep-2020 11:06
    Eh, maybe.  Last I heard, CDRH was trying to position the De novo as merely a classification process, not an approval process.  I personally think classification falls somewhere between no and half a brain.  Not sure what to make of the notion that CDRH might find classification exhausting.

    ------------------------------
    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Mebane, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
    ------------------------------



  • 9.  RE: De Novo Submission

    This message was posted by a user wishing to remain anonymous
    Posted 02-Sep-2020 09:42
    This message was posted by a user wishing to remain anonymous

    I have been following this post and appreciate all of the information provided. I have been having difficulties finding product codes for SaMDs. Do they follow the same process as Sergio outlined above? Thank you for all of your help with this topic!


  • 10.  RE: De Novo Submission

    Posted 02-Sep-2020 09:23
    Edited by Julie Omohundro 02-Sep-2020 10:53

    It sounds like you may be equating to a CER-type search for clinical data, where the search is a key focus.  I don't know if CDRH treats it that way, but it definitely should not do so, because it's not the same thing at all. So different in so many key ways, I won't even begin to compare, since you don't need to know that to go forward.

    I see this as FDA wanting applicants to do the "search" instead of it having to do it, much like it wants applicants to write the summary of its decision. Like that task, this is a pretty safe kickback of responsibility, because few (any?) companies are angling to do a De novo when they can do a 510(k) instead  Usually the motivation is the other way.

    If there is a predicate, it has to have the same intended use.  This narrows your "search" considerably.  I would not describe the search in a CER/literature database kind of way.  I would describe the "search" you must have already done, which I think probably started with ortho/cardio/whatever devices and then went to therapeutic/diagnostic/prosthetic/whatever subgroups are available within that area.  The only real "search" is usually of the classification regulations and product codes within that narrow scope.  And I would have called it a "review," not a "search."

    So I would say something like the intended use of device x is [e.g., ophthalmic surgical]. A review of the ophthalmic surgical] classification regulations and product codes did not identify another device with the same intended use. I might briefly put some substance here, depending on the situation, like citing 2-3 that you thought were closest (if any) and why they didn't fit.  And dress them up by citing the specific regulation and/or product code. 

    Or, if you found one or a few with the same intended use, but, due to technological differences, thought your device would not be at least as safe and effective as the potential predicate device or would "raised new questions of safety and effectiveness," whatever that mean, I'd explain that.  And then I'd move on to risk, which I agree with Richard is usually the big question.  Because many many companies would prefer to do a De novo over a PMA, and therefore CDRH should be looking closely at this.

    I do not see CDRH rejecting a De novo for review, much less for market, just because of an inadequate "search," a poor choice of words on its part, IMO, because it's going to evoke something different for people who have been swimming in the CER swamp.  I'm not sure it can reject it, legally.  I think it has to be able to point to a specific predicate, not an inadequate search.  But I can see it declining to review a De novo if the submission didn't address the question of a potential predicate at all.

    I see this as a high-level time-saving cut on CDRH's part, designed to screen out De novos submitted by the clueless.  When a client says they want a 510(k), the first question I ask is Have you identified a predicate?  I don't actually care if they have identified a predicate or not  What I want to know is whether they know that they need a 510(k).  I have spared any number of companies from being contractually obligated to pay me for preparing 510(k) that they didn't need and that FDA wouldn't have have accepted.  So, perhaps it's just because I'm coming at it from that experience, but that's pretty much how I see this "search."  It's not the search, but the underlying knowledge and understanding that CDRH is looking for.



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    Julie Omohundro, ex-RAC (US, GS), still an MBA
    Principal Consultant
    Class Three, LLC
    Mebane, North Carolina, USA
    919-544-3366 (T)
    434-964-1614 (C)
    julie@class3devices.com
    ------------------------------