Hello, my name is Lieutenant Commander Kimberly Piermatteo. I am a Regulatory Operations Officer within the Center for Devices and Radiological Health. I have held various positions within the center, including being a premarket reviewer within the Office of Device Evaluation. During today's presentation, we're going to cover the fundamentals of the 510(k) program.

A 510(k), which is also referred to as a premarket notification, is one of the major pathways for bringing device to market. Actually the 510(k) is the most common premarket submission for medical devices. During today's presentation, we are going to cover the following learning objectives: I'm going to provide you with an understanding of medical device classifications and how classifications apply to 510(k)s;  we're going to cover what is a 510(k) and when it is required;  and the different types of 510(k) submissions: what should be included in a 510(k); the actual content; and what should be submitted to the FDA.

We're also going to talk about the 510(k) submission process and the timeline on how and when the FDA will communicate with you during the review of your 510(k). And lastly, we'll cover what are 510(k) decisions and what they mean.

So let's begin. Let's talk about device classification as it relates to 510(k)s. The FDA regulates medical devices based on risk. Class I devices are considered low risk devices. These devices are subject to general controls. Most, but not all, Class I devices are exempt from the premarket notification process. Class II devices, which are considered moderate risk devices are subject to general and special controls. Most, but not all, Class II devices require a premarket notification. This is going to be topic of our presentation today mostly.

Now, Class III devices are considered high risk devices and these are subject to general controls and premarket approval. Most product codes are found on all 510(k) clearance letters. This can be extremely useful to you as you can search for relevant products that have similar product codes. Within this slide I provided you references to the guidance document on medical device classification product codes, which provides additional information on what product codes are and how they can be used, as well as my favorite reference is a product classification database.

This database can be extremely useful. It is a public database and it provides you a wealth of information on the appropriate regulatory pathway for different devices. On this slide, I've provided you examples from the product classification database. This example is for infusion pump and as you can see, this is an output from the product classification database, which lists a whole bunch of information, including that three letter product code, FRN.

And what is even more useful, it specifically outlines a submission type on the product classification. So here, as you can see where the blue arrow is pointed the submission type, is for a 510(k). For an infusion pump, you would submit a 510(k) for this type of product.

So what you do if you can't determine the appropriate device classification? You have done due diligence and you’ve looked in the product classification database, but you’re still unable to determine the appropriate classification for the product. You might want to consider the 513(g) program. The 513(g) program is a request for information to FDA. The FDA will respond by providing what they think is appropriate regulatory pathway for your device. There are a few caveats to the 513(g) program that I'd like to provide you. There is a 513(g) user fee. So please keep that in mind when you are preparing to submit the 513(g). FDA responses to 513(g)s do not constitute FDA clearance or approval. If you submit your 513(g) and the FDA responds with the appropriate regulatory pathway, you still must comply with that pathway, such as submission of  a 510(k) or the submission of premarket approval application.  On this slide, I provided you references to 513(g) program and the user fees associated, and please refer to those for additional information.

Next, let’s talk about the actual 510(k) program. Let's first talk about what a 510(k) is. As I mentioned before, 510(k) is also referred to as a premarket notification. The reason why a Premarket Notification is also referred to as a 510(k) is because it actually refers to the section 510(k) of the Federal Food, Drug and Cosmetic Act. That is why people often say 510(k) and Premarket Notification interchangeably. Within 21 CFR, which stands for Code of Federal Regulations, 807 sub-part E, this actually outlines the information required in the submission of your 510(k).

A 510(k) is considered a marketing clearance application, therefore, the FDA clears 510(k)s. The clearance is based on the determination of Substantial Equivalence. Now on the contrary, a 510(k) is not just a form. A 510(k) can be an entire submission that can be hundreds of pages long. It all depends on the device and what needs to be submitted to demonstrate Substantial Equivalence.  A 510(k) is not establishment registration or device listing, and a 510(k) is not a premarket approval. Therefore, it’s inappropriate to say that FDA has cleared your 510(k), and therefore your product is FDA approved. Only products or devices approved through the premarket approval process are considered FDA approved. Keep in mind that a 510(k) receives FDA clearance and therefore, it is FDA cleared.

Now let's talk about Substantial Equivalence. This is the bread and butter of the 510(k) program. Substantial Equivalence is basically the demonstration that your new device, compared to a predicate device, has the same intended use and the same technological characteristics, or it has the same intended use and the differences in technological characteristics do not raise different questions about safety and effectiveness. It is important to note that Substantial Equivalence is the whole point of the 510(k) program and that is what you are trying to demonstrate in your submission. So what is a predicate device? You are demonstrating Substantial Equivalence. So you have your new device and a predicate device. The predicate device is actually a legally marketed device that is typically cleared through the510(k) process, and this is used for comparison of your device, the new device, to the predicate device,  and this is the premise of Substantial Equivalence.

On this slide, I’ve provided you multiple references to the 510(k) program. Specifically, I want to draw your attention to the final guidance, the 510(k) program, which is titled Evaluating Substantial Equivalence in Premarket Notification. This is an extremely important guidance document for anyone who’s participating in the 510(k) program, and I recommend you take the time to review the guidance thoroughly. I will be referring to this guidance throughout the rest of the presentation, so please make a note of the link to this guidance.

Additionally, there was a public CDRH webinar which provides additional information as well, and then the link at the bottom on How to Find and Effectively Use Predicate Devices is also helpful. The 510(k) decision-making flow chart, I don't expect you to be able to read this flow chart right now. We'll go over the decision points on the next slide.

But take your attention to Appendix A of that 510(k) guidance document that I referred to on the previous slide. This decision-making flow chart is what you should be referring to when demonstrating your Substantial Equivalence. Let's go through each of those decision points. This is what the premarket reviewers look at what they look at your 510(k) submission to make sure you are following through the flow chart and demonstrating substantial equivalence.

The first point, or decision point - is the predicate device legally marketed? Therefore, has the predicate device received the appropriate clearance or approval as necessary? The second decision point is do the devices have the same intended use? This is very important, because it is going to be difficult to demonstrate equivalence to a predicate device that has a different intended use. The third decision point is - do the devices have the same technological characteristics? And if they do not have the same technological characteristics and they raise different questions of safety and effectiveness, then you’re going to move through decision points four and five.

If there are differences, again, in decision point five, it’s two parts. You are going to provide the methods acceptable for your performance testing to demonstrate Substantial Equivalence and you’re going to provide data that is used to demonstrate that Substantial Equivalence. So the reviewer is going to look to make sure you’ve addressed these decision points. Please take the time to review the flow chart and make sure the 510(k) submission provides information necessary.

So when a 510(k) is typically required? A 510(k) is typically required in three scenarios. The first is if you are introducing a new device to the market for the first time.

The second could be changing the indications for use of a previously cleared device, and the third could be making significant modifications to a previously cleared device. In these situations, this is when a 510(k) would be required, and you would require 510(k) clearance before you could market the product. On this slide I provided references.

One of the main questions we receive is you’ve made changes to your product and whether or not it requires submission of new 510(k)? So if you have questions on whether or not you have made a modification to an existing device, please refer to the following references.

There are three types of 510(k) submissions. There is a traditional 510(k), an abbreviated 510(k), and a special 510(k). We're going through each one specifically. For a traditional 510(k), you must submit the required elements of 21CFR 807.87. These are typically the administrative requirements, such as the business name, the trade name, things like that.

The traditional 510(k) relies on the demonstration of Substantial Equivalence. It’s important to note that a traditional 510(k) can be used under any circumstance. The abbreviated and special 510(k) can only be used if certain criteria are met. An abbreviated 510(k) must also include the required elements of 21 CFR 807.87. But an abbreviated 510(k) relies on the use of guidance documents, special controls and recognized standards. Under certain conditions, sponsors may not need to submit test data in an abbreviated 510(k) because you are following the FDA recommendations and guidance documents, or recognized consent of standards. So, that is when an abbreviated 510(k) may be appropriate.

A special 510(k) must also include the required elements of 21 CFR 807.87. However, a special 510(k) is appropriate when you are making device modifications to a manufacturer's own legally marketed device. Therefore, you are making modifications to your own product. You own the predicate device. It is important to note, also, for a special 510(k) to be appropriate, the modification may not affect the intended use or the fundamental scientific technology of the device. Because the reason for this is the data is not typically submitted with a 510(k), or special 510(k). On this slide, I've also provided with you with additional references on how to prepare a traditional, abbreviated, and special 510(k), as well as the 510(k) screening checklist and a link to the appropriate 510(k) forms.

What do you do if you have a low or moderate risk device with no identifiable predicate device? So have you taken the time and done due diligence, and are unable to identify an appropriate predicate device?  You may want to consider a de novo. For more information on the de novo program, please refer to other modules within CDRH Learn.

Next let's talk about the content of a 510(k) and what should be submitted in your 510(k). On this slide, I have provided you various bullets on what should be included in the content of your 510(k). There are various administrative requirements, certain forms and cover letters. But specifically, during this talk we'll go over the highlighted aspects in more detail. Let's first start off by talking about the intended use and the indication for use. The intended use is the general purpose of the device or its function, and encompasses the indications for use. So the intended use is a broad term, and indication for use is encompassed within the intended use. The indications for use actually goes into more detail, and describes the  disease or condition the device will diagnose, treat, prevent, cure or mitigate, including a description of the patient population for which the device is intended.

You want to make sure that you're intended use and indications for use is consistent throughout your 510(k). Make sure they’re both the same in your indications for use statement, proposed labeling, your instructions for use, etcetera. There is a recommended format for the indications for use statement, please refer to form FDA 3881. And when you submit that form, make sure you identify whether or not your product is considered prescription use or over the counter.

The next aspect of the content of your 510(k) should be your 510(k) summary. The 510(k) summary is a high level discussion of the content within your 510(k). Within your 510(k) summary, you should cover the elements covered in 21 CFR 807.92. Your 510(k) summary should include sufficient detail to provide an understanding of the basis for your determination of Substantial Equivalence. During the review of your 510(k), the FDA will verify the accuracy and completeness of your 510(k) summary. For more information on what should be included in a 510(k) summary, please refer to that final guidance - The 510(k) Program, specifically Appendix B, which covers the 510(k) summary document requirements as well as provides a great example of a complete 510(k) summary.

Next let's talk about FDA recognized consensus standards. This is a voluntary program used to simplify and streamline the 510(k)review process. Sponsors can declare conformance to consensus standards in order to help the review process. Sponsors should document the extent of their conformance in their 510(k) application, via the form FDA 3654. If you have additional questions regarding the standards program, please refer to the following guidance, as well as, there is a public recognized consensus standards database which you can search for FDA recognized consensus standards. FDA guidance documents - this is very important to understand because FDA guidance documents actually represent FDA’s current thinking on a topic. FDA guidance documents can be device specific or they can be general, and apply to multiple different devices. However, guidance documents do not create or confer any right for, or on, any person, and do not bind the FDA or the public. So really, the guidance document provides FDA’s current understanding or current thinking. Alternative approaches may be used that are outside of the guidance documents if those approaches satisfy the requirements of the applicable statutes and regulations. There is a public FDA guidance document database which you can search for FDA guidance documents.

I want to recap and go back to the product classification database which I told you I think is invaluable tool. On the bottom of that product classification for the infusion pump under the product code, FRN, was also listed these FDA recognized consensus standards and guidance documents. As you can see, they are specific to infusion pumps, so you can refer to them if you are developing a 510(k) submission for  infusion pumps. It can be extremely helpful, and please refer to the product classification database to get this additional information.

Next within your 510(k), you should make sure you include a detailed device description. Within your 510(k), you want to include the description of the device design, including anything that you think is important for the reviewer to be able to understand the intended use and the purpose of your product. You can include anything from figures to diagrams, anything which would be helpful to describe your device. Additionally, you want to include a listing of material, specifically the patient contacting material because that will indicate what type of biocompatibility testing would be appropriate. Additionally, within your device description, you want to include energy sources, such as battery or ac power, and include any key technological features.

Within your 510(k), you also want to include a detailed Substantial Equivalence discussion. The Substantial Equivalence discussion is the foundation of your 510(k). Please refer back to the 510(k) decision-making flow chart, and go through each of the decision points so that you are clear, and the reviewer is clear, as to how you are demonstrating Substantial Equivalence. The 510(k) review standard is again, it’s comparative. So you’re comparing your new device to your predicate device.

Within the 510(k) Program final guidance, it addresses specific points that I want to make note of during this presentation. The first one is that multiple predicate devices are okay only under certain circumstances. For additional references or examples on when multiple predicates may be appropriate, please refer to the guidance.  It is important to note that split predicates are inconsistent with the 510(k) regulatory standard. And lastly, within the guidance, it addresses a new term called Reference Devices. Reference devices may be used to support scientific methodology or standard reference values. Reference devices are not predicate devices. Therefore, reference devices typically won't come into your 510(k) until around decision point four. Please keep that in mind when providing your Substantial Equivalence discussion.

Within your 510(k), you should provide your proposed labeling for your device. Your device labeling should comply with requirement of 21 CFR 801. Copies of all your proposed labeling are recommended, including your package insert, service manuals, instructions for use, advertising and/or promotional materials. The directions for use should include your specific intended use statement and any warnings or contraindication or limitations for your device. Your labeling in your 510(k) should be submitted as a final draft. Copies of your predicate device, device’s labeling, is recommended but is not required. If you have additional questions or need further clarification, please refer to the Introduction to Medical Device Labeling at the link provided on this slide.

Next, we're going to talk about performance testing. Performance testing can be bench, animal or clinical. Performance testing is actually determined specifically to the complexity of your device and its intended use. So every 510(k) is going to have different performance testing depending upon the difference in the technological characteristics, or the differences in the new device compared to the predicate. I recommend that you consider FDA guidance documents, especially the device specific guidance document, which may provide recommendations on appropriate performance testing.

You may consider comparative testing to demonstrate Substantial Equivalence – which could be side by side comparison testing of your device compared to the predicate, but that is not required. If you are unable to obtain the actual predicate device, consider comparative testing in a sense of a table which outlines the comparison of the two different specifications and their intended use, etcetera. Within your performance testing, you should include your test methods, your acceptance criteria, and your test results for review.

I want to make a specific note on performance testing - clinical performance testing. Clinical testing is most often not required for 510(k) submissions. However, clinical data may be requested in the following situations -- when you have a new or modified indication for use, clinical testing may be needed; if you are making significant technological changes, that may also require new clinical data; or when nonclinical testing methods are limited or inappropriate because of the indications for use or device technology. Please refer to the 510(k) program final guidance for additional examples and explanation on when clinical data may be appropriate.

So when we're talking about content of 510(k), to wrap up with key considerations, make sure your information is complete and organized, make sure your 510(k) is organized, include a table of contents, and make sure you use tabs and paging appropriately. If you can use tables and graphs, this can be helpful for the reviewer during their review, and use visual aids whenever possible. Within your 510(k), you want to make sure you clearly identify basic 510(k) requirements, such as a 510(k) summary or indications for use form. And make sure that you're consistent throughout your 510(k) submission.

As we mentioned earlier about intended use and indication for use, make sure they are consistent throughout your 510(k). Again, please follow any applicable guidance document or device specific checklist; they are there to help you prepare your 510(k). On this slide, you have some references to the content of 510(k), as well as 510(k) formatting tips. Please refer to those for additional information.

So lastly, for the content of a 510(k), I want to provide information regarding the pre-submission program. There is a guidance document titled “Request for Feedback on Medical Device Submissions, the Pre-submissions Program and Meetings with the FDA Staff”. This can be a valuable program. It is a way for you to obtain fee back from the FDA before the actual submission of your 510(k).

But typically, a Pre-sub for a 510(k) is ONLY appropriate for unique situations, such as when you may need clinical data to support your demonstration of substantial equivalence. Through the Pre-submission program, you would submit a formal written request to the FDA and you would request a formal written response, a meeting, or a teleconference to address your concerns. Because this is a formal written request, it is subject to e-copy requirements, which we'll discuss during the submission of a 510(k). But it is important to note they are subject to eCopy. For additional information on the Pre-submission program, I have provided you a link to the guidance on the slide and public CDRH webinar on Pre-submissions and Meetings with FDA Staff.

Now let's talk about the 510(k) submission process. Before we get into the actual time line, I want to provide you with some important notes before you submit your 510(k). The first is your submission to the FDA. You must submit two copies of your 510(k). One of those two copies must be submitted in electronic format, or what is also referred to as an e-Copy. The FDA does not return your 510(k) submission after its review, so you will not get back the hard copy. When you mail your 510(k), please make sure you mail it to the appropriate Document Control center, to the address provided on this slide. For additional references, refer to our addresses for submission link, also provided on the slide.

I referred to the eCopy and so I'd like to talk about the eCopy program a little bit so you have a better understanding. A valid eCopy is a requirement for premarket Submissions, including the 510(k). An eCopy is defined as an exact duplicate of the paper submission. An eCopy is accompanied by a paper copy of the signed cover letter and the complete paper submission. For your 510(k), you will submit one electronic copy or e-Copy and one paper copy. If you have additional questions regarding the requirement of a valid eCopy, please contact our eCopy experts and refer to the eCopy program for medical device submissions website, which provides a great instructional video on  the appropriate nomenclature for your submission and things like that.

Also, before you submit your 510(k), you have to submit your user fee. 510(k) submissions are subject to user fees. Your user fee must be received on or before the time the application is submitted. FDA will not accept the 510(k) for filing if the fee is not paid. There is a standard user fee, and a small business reduced user fee. If you believe that you are a small business, which makes less than $100 million in sales, you must submit your Small Business Determination qualification first. If you submit the standard 510(k) user fee and then subsequently later get a small business determination qualification, the FDA will not refund you the difference.

So please make sure that if you think you are a small business, that you get your Small Business Determination number first, so that way you are eligible for the reduced fee. On this slide I've provided references to 510(k) review fees, as well as the medical device user fee Small Business Qualification and Certification guidance. Please refer to those if you believe you are a small business.

Next let's talk about the 510(k) submission process. The 510(k) submission process is very important to understand because this is going to be how and when the FDA communicates with you during your review. So that way, you are informed and your company is informed as to when your 510(k) and where your 510(k) is at. This timeline has been simplified, and please keep in mind, the days are in calendar days. For the actual content of the 510(k) submission process, please refer to the 510(k) submission process website. This website provides the timeline, as well as additional links and resources to guidance and other things that help simplify the timeline.

Let's begin with 510(k) submission process. The timeline.  Day 1 is the day FDA receives your 510(k) submission. By Day seven, the FDA will either send you an acknowledgment letter, or a hold letter. If you receive a hold letter, which means that there are issues with your user fee and/or eCopy. So if you receive a hold letter, your 510(k) will not proceed to be accepted for filing until you have resolved the user fee and/or eCopy hold issue. By Day 15, after your 510(k) has passed through the user fee and eCopy, the FDA will conduct an acceptance review. By Day 15, you will find out from the FDA if your 510(k) has been accepted for substantive review or if it has been placed on Refuse to Accept Hold.

Refuse to Accept Hold or the Refuse to Accept Policy is outlined  in the guidance and link provided on this slide. I recommend that you review that guidance thoroughly. It provides a great checklist so that you can make sure you're meeting all of the administrative requirements of your 510(k), and that is the purpose of the Refuse to Accept Policy - to make sure that your 510(k) is administratively complete and that the reviewer can conduct a substantive review.

The FDA clock begins on the date receipt of when your 510(k) is accepted for review. So if your 510(k) does not pass the RTA hold, your 510(k) will be put on hold until you submit the necessary information. By Day 60, the FDA will conduct their substantive review. And by Day 60, the FDA will communicate with you as to whether or not your 510(k) will proceed through Interactive Review or they will make an additional information request.

So a Substantive Interaction that they will have with you by Day 60, as I mentioned, can be that your 510(k) will not be placed on hold, and the outstanding deficiencies resolved via Interactive Review, or that your 510(k) will be placed on hold and you will receive a formal additional information request, which identifies the outstanding deficiencies that need to be addressed. Let's go into those specifically. Interactive Review is an informal interaction between FDA and the submitter during the review of the 510(k). Interactive review requests do not stop the FDA clock. That can be beneficial, because it prevents unnecessary delays and may reduce the overall time to decision, and it ensures timely responses from submitters are received. So the reviewer will determine whether or not Interactive Review is appropriate.  Please note, though, that Interactive Review correspondence is not subject to eCopy requirements unless you submit information that is needed for the Interactive Review through the Document Control Center. So anything that is submitted to the Document Control Center must have a valid eCopy.

Additional Information requests are formal requests. Additional Information requests are made via e-mail. However, that does not stop the reviewer from contacting the 510(k) submitter to discuss the decisions in detail.  However, the reviewer will follow-up with formal e-mail to place the submission on hold. So additional information requests are Formal, and they are subject to eCopy requirements.  Because they are formal, they do stop the FDA clock. So a company, or a 510(k) submitter, has up to 180 days to provide a complete response to the AI request to the Document Control Center. It’s important that you note that you have 180 days to respond. If you submit your file on day 179 and you do not pass the eCopy requirements, your file may go over 180 days and your 510(k) may be withdrawn.

So please account for that when preparing your response for additional information. Next, by Day 90, FDA will hopefully issue a MDUFA decision on 510(k). MDUFA III’s performance goals are for a traditional and abbreviated 510(k), 90 FDA review days, and for special, 30 days. If you do not receive a MDUFA decision by Day 90, the FDA will communicate with you via missed MDUFA decision communication by Day 100. This communication will outline the outstanding review issues with your 510(k).

Now let's talk about 510(k) decisions. 510(k) decisions - you can receive a Substantially Equivalent Decision, or Non-equivalent Decision. If you receive a Substantially Equivalent Decision, you can then market your product. You received 510(k) clearance. It is important to note, though, once you received 510(k) clearance, you now have a valid 510(k) number, and you should complete your establishment registration and device listing. Please refer to the other modules on CDRH Learn for additional information on how to comply with registration and listing requirements.

If you receive a NSE or a Non-Substantially Equivalent Decision,  you may have to resubmit another 510(k) with new data. It may be appropriate for you to submit PMA, a de novo, or reclassification petition.

So why might you receive an NSE decision? The first reason may be you don't identify an appropriate predicate device. Either your predicate device was not legally marketed, or not appropriate. And it could be that your predicate device has new intended use compared to predicate device.

Or you may receive an NSE because the differences in technological characteristics compared to the product device do raise different questions regarding safety and effectiveness.

You may also receive an NSE decision if you do not demonstrate that your device is as safe and as effective as your predicate, so make sure in your 510(k) that you go through the Substantial Equivalence discussion and make sure you are addressing the decision point within the flow chart.

What happens after your device is cleared? The following are posted on the FDA public 510(k) database:  your Substantial Equivalence determination letter; your Indication for Use form; and your 510(k) summary, if one is provided or if you have provided a 510(k) statement instead. Please note for the 510(k) statement, submitters must make available all information included, and their premarket notification on safety and effectiveness within 30 days of a request by any person.

In summary, we have covered a lot of aspects regarding the 510(k) program during the presentation. We have covered the fact that the appropriate classification for a device will indicate whether or not 510(k) clearance is required before the device can be legally marketed. We’ve gone over that the 510(k) standard is comparative; therefore Substantial Equivalence must be demonstrated for a new device compared to a legally marketed predicate device. We also covered in depth what type of content should be included in your 510(k) to demonstrate the safety and effectiveness of the new device compared to the predicate device, and we went over the timeline for which the FDA will communicate with submitters during the review of 510(k)s. We talked about 510(k) decisions and if a 510(k) is found Substantially Equivalent that it can be legally marketed in the United States. This slide provides you with additional resources for obtaining information about medical device regulation, so please refer to that if you need additional assistance.

I hope that this presentation has provided you with fundamentals of the 510(k) program and thank you for watching.