United States: Podcast: Non-binding Guidance: Breakthrough Devices Program

Last Updated: September 23 2019
Article by Gregory H. Levine and Kellie Combs

The sixth installment of Ropes & Gray's podcast series, Non-binding Guidance, continues our two-part discussion on FDA expedited review programs. In this episode, Ropes & Gray lawyer Kellie Combs interviews her partner Greg Levine, who provides an overview of FDA's new Breakthrough Devices Program. This program, which was finalized in late 2018, aims to expedite the development and FDA premarket review of devices used in the treatment or diagnosis of serious or life-threatening conditions. The Breakthrough Devices Program provides a variety of benefits to manufacturers, including priority review and more frequent and efficient feedback from FDA during the submission and review process, so that devices receiving breakthrough designation can reach the patients who need them quickly and efficiently. In this episode, Greg dives into the program's eligibility criteria, benefits, when to apply, and some of the practical considerations associated with the program. Additionally, Kellie and Greg discuss recent trends and developments affecting breakthrough devices and provide examples of devices that have recently received breakthrough device designation or that were approved or cleared as breakthrough devices. Tune in to this discussion to learn more about the program and its impact on the medical device industry.

If you missed last week's episode on FDA expedited review programs for drugs and biologics, please check it out here.


Transcript:

Kellie Combs: Hi. I'm Kellie Combs, a partner in the life sciences regulatory and compliance practice group at Ropes & Gray, based in our Washington, D.C. office. Welcome to Non-binding Guidance, a podcast series from Ropes & Gray focused on current trends in FDA regulatory law, as well as other important developments affecting the life sciences industry. I'm here today with my partner Greg Levine. Today's podcast will talk about FDA's Breakthrough Devices Program. In addition to providing an overview of the program, Greg will talk about eligibility criteria, benefits, when to apply, and some of the practical considerations associated with the program. Greg, can you start off by providing an overview of the Breakthrough Devices Program?

Greg Levine: Thanks, Kellie. There's just one single program for expedited review of medical devices – it's called the Breakthrough Devices Program, and that applies both to new devices and to device-led combination products. "Device-led" means that the combination product as a whole is subject to FDA pre-market review through one of the device pathways – the 510K, PMA, or De Novo classification pathways. Congress mandated this program in the 21st Century Cures Act; it was passed in 2016. And the specifics of that program were laid out in FDA guidance that the Agency finalized in December of last year, December 2018, so this is a relatively new program. The current program will replace two existing FDA programs – the Expedited Access Pathway, or the EAP, and the Priority Review Program. Unlike the breakthrough program, the EAP had been limited to devices subject to PMA approval. The newer program is broader in that it includes both De Novo and 510K devices as well. If a device had previously received EAP designation but had not yet been approved, FDA has now deemed that device to be a breakthrough device under the current program.

Kellie Combs: Greg, what are the eligibility criteria for the program?

Greg Levine: At a high level, the criteria are similar to the programs that FDA has had in place for a number of years now for expedited review of drug products. These focus on providing patients with timely access to products, to drugs, in that case, for unmet medical needs in serious or life-threatening conditions, but there are a lot of differences in the specifics. For the device program, the overall structure is that there's one over-arching statutory criterion, which is that the device must provide for more effective treatment or diagnosis of a life-threatening disease or irreversibly debilitating human disease or condition. And then the second criterion, which is showing that at least one of four additional factors is met. So I'll go over these individually.

First, as I said, the device must provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions. As FDA has interpreted that statutory language, "more effective" means that there's a reasonable expectation that a device could provide more effective treatment or diagnosis for the disease or condition identified in the applicant's proposed indications for use of the device relative to the current U.S. standard of care. To establish the required reasonable expectation, you need to show that the device can have both technical success and clinical success. A life-threatening disease or condition is one where the likelihood of death is high unless the disease or condition is interrupted, so, for example, an acute stroke or an MI. And an irreversibly debilitating disease or condition is one associated with morbidity that substantially impacts daily functioning, such as certain cancers or ALS.

Now assuming the first criterion can be satisfied, as I mentioned before, you then have to show that you can meet one of four additional criteria, the first being that the device represents a breakthrough technology. This would mean that the device itself is novel technologically or that it represents a novel application of existing technology that has the potential to lead to clinical improvement in diagnosis, treatment, cure, prevention, or mitigation of a life-threatening or irreversibly debilitating disease or condition. So that's one of the four.

Another would be that there's no approved or cleared alternative for the device. This means that there's no alternative drug, biologic, device, or combination product that has received FDA marketing approval after pre-market review or clearance for device for the same indications proposed for the new device. In making that determination, it's irrelevant that there might be an off-label use of a product on the market for that indication or that another product is on the market for that indication but it did not require any pre-market review by FDA. So examples of those types of products would be an exempt device or perhaps an OTC monograph drug.

Alternatively, so this would be the third out of the four, the device could offer significant advantages over existing approved or cleared alternatives. This would apply if there's a potential compared to existing approved or cleared alternatives to reduce or eliminate the need for hospitalization, to improve the quality of life, facilitate patient's ability to manage their own care, or establish longer-term clinical efficacy, for example.

And then lastly, the fourth out of the four possibilities in this prong of the test is that availability is in the best interest of the patient. And obviously that's very broad language that Congress wrote into the statute, but as FDA had interpreted it, this criterion looks at whether the proposed device for the proposed indications would provide some other type of public health benefit not described or addressed by the three other criteria. So, for example, if a device has benefits for patients unable to tolerate available therapy, or if it provides an additional benefit that might improve patient compliance, or addresses a shortage of a particular device, any of those would be examples of these types of other public health benefits.

FDA describes these criteria in detail in the guidance that it put out in December 2018. And one interesting aspect of that guidance is that FDA gives examples of older devices that, had the Breakthrough Device Program existed at the time they were cleared or approved, would have been eligible for the program. And so to provide just two examples of that, FDA says that, for example, a transcatheter heart valve, when that first came on the market, would have been a product where the technology itself would have been considered a breakthrough. Second is, FDA says that a device for earlier diagnosis of pre-eclampsia would be one that offers significant advantages over existing approved or cleared alternatives. I find this guidance to be particularly useful compared to some other FDA guidances as a general matter in that includes a number of specific examples of that nature.

Kellie Combs: Great. Thanks, Greg. And what about the features and benefits of the program?

Greg Levine: First, breakthrough devices automatically qualify for priority review. That's why, as I mentioned earlier, the breakthrough program replaced not only the EAP, the Expedited Access Pathway, but also the Priority Review Program. Second, breakthrough designation generally allows for more frequent and efficient feedback from the FDA during the submission and review process. So in addition to priority review status, an applicant that succeeds in getting breakthrough status can benefit from a number of other expedited procedures that FDA has put in place. One of these FDA is calling "sprint discussions" – that's a new term under the guidance. These are discussions with a goal of reaching mutual agreement between the applicant and FDA on a specific topic within a set time period that the parties agree on. There's no limit on the number of sprint discussions you can have in the course of review for one device, although FDA recommends, and I think common sense dictates, that you would only want to handle one of those at a time. Another would be a Data Development Plan – this is a high-level document to ensure a predicable device assessment and review, and it outlines the data collection expectations for the entire lifecycle of that product. So that would be a document that would be agreed on between the applicant and FDA. Another type of benefit would be a Clinical Protocol Agreement – this would be a written agreement for clinical protocols required for that device to be approved or cleared that would be binding on FDA and the sponsor with certain limited expectations I won't get into here. This is similar to the special protocol assessment that exists for biological products and has been in place for some time in that area. Lastly, in this list of potential benefits, there are more regular status updates or more frequent status updates than otherwise would be the case. So FDA and the sponsor will agree to regular status updates to discuss general progress on the application and next steps or plans for future discussions. The topics, format, and participants for these updates can vary from product to product and application to application. And then lastly, FDA has also committed to expedited manufacturing and quality system reviews for breakthrough devices. This is going to apply, for the most part, to PMA devices. But any device that's subject potentially to a pre-approval inspection could benefit from this aspect of the program.

Kellie Combs: Now that we've talked about eligibility criteria, and features and benefits of the Breakthrough Devices Programs, let's talk about the logistics. So when and how should a sponsor apply for breakthrough designation?

Greg Levine: Most critically is the when piece of that, and a sponsor has to request designation any time before it makes its submission for pre-market review. So if you wait until the time of submission of your application, whether it's a 510K, or a De Novo application, or a PMA, it's too late by that point. As far as the how, sponsors can request designation by submitting a "Designation Request for Breakthrough Device" Q-Submission, what FDA calls a Q-Submission under its pre-submission guidance for medical devices. These submissions for breakthrough devices are not subject to the acceptance review period like most pre-submissions are, so there's not a period of time that FDA has to evaluate whether to accept that submission like it does for most other types of pre-submissions. In such a designation request, you should only include this designation request in the Q-Submission, so it's not a document where you would be covering multiple topics – and that December 2018 guidance has some additional information and a template for making these kind of submissions. It's also important to understand that breakthrough device designation may be granted for multiple devices that have the same proposed intended use – there's no restriction on how many devices can get the designation. But once one device has received approval, clearance, or De Novo authorizing a given indication, the next applicant, the next person that seeks breakthrough designation for that indication, is going to have a higher bar because there's something else on the market for that use.

Kellie Combs: Greg, what happens after you submit your request?

Greg Levine: FDA intends to request additional information within 30 days of receiving such a request and grant or deny the request within 60 days. If a request for breakthrough designation is denied, then the applicant can appeal under the formal appeals process that's in place for medical devices, which is called the 517A process.

Kellie Combs: Greg, for breakthrough devices, what are some recent developments and trends that we should be aware of?

Greg Levine: One important development to be aware of is that there have been many more applications under this new program, the Breakthrough Devices Program, than there were under the old EAP program. As I mentioned before, that program had been limited to Class III PMA devices. The early signs looked very positive, both in the level of industry interest and in FDA's commitment to making this program work. For example, as of January 2019, FDA had granted 112 breakthrough designation device requests. Examples include devices intended for the treatment of Alzheimer's disease and dementia, oncology applications, opioid abuse, and others. And in 2018, FDA approved or cleared nine devices with breakthrough designations. Just in August of this year, FDA designated five devices for breakthrough designation and approved one other device, so there does seem to be quite a bit of momentum behind this program.

Kellie Combs: Greg, what are some examples of devices that have been recently approved through the program?

Greg Levine: Well, the one that FDA announced most recently on August 16, was a PMA approval for the BAROSTIM NEO system. This is a device intended for improvement of symptoms in patients with advanced heart failure who are not suited for treatment with other heart failure devices, such as cardiac resynchronization therapy. FDA designated this device as a breakthrough product because it treats a life-threatening disease, heart failure, and addresses an unmet medical need because there are patients who can fail to get adequate benefits from the standard treatments and don't have alternative treatment options.

Another product also that was a PMA-approval under the program, and actually was a holdover from the other program – it originally had been designated under the EAP program – was called the Optimizer Smart System. This is a PMA-approved heart failure device, so another cardiac-related device, that uses cardiac contractility modulation to improve heart function. This was the first device in the Breakthrough Devices Program to go before an advisory panel. The advisory panel recommended device approval, despite some concerns about the adequacy of the clinical trial data. And that PMA was approved in March 2019 – and in that case, FDA required a follow-up study as a condition of approval.

And then, lastly, I want to mention one other which was not a PMA device, which is called the Brain Trauma Indicator from Banyan Biomarkers. This was a blood test that detects concussion and is designed to reduce the need for CT scans to detect intracranial lesions. It was authorized for marketing through the De Novo pathway and, according to FDA, De Novo review and Class II designation was completed in less than six months, which is quite an accelerated process. Now, device development for this product was supported by the U.S. Army, so it's possible that that had some influence in FDA in getting them sort of some extra attention, but that's a product that was not a PMA product that was cleared through this program.

Kellie Combs: And finally to close this out, what are the practical considerations to keep in mind with the breakthrough devices program?

Greg Levine: I'd say first and foremost would be to communicate early and often with FDA. As I said before, this is not a program where you can wait until late in the process, or at the time of approval or clearance to apply for. So you'd be wanting to engage in early discussions with the FDA, if possible, to talk about eligibility criteria and apply for designation. Some other things to be aware of, as I mentioned before, if it's a product that would undergo pre-approval and a pre-approval inspection for quality system regulation compliance, you're going to want to make sure that you have your manufacturing process up and running and ready for such an inspection so that you can actually reap the benefits of an accelerated inspection schedule. Similarly would be to anticipate FDA's needs to inspect clinical study sites or to do a sponsor inspection. So again, if you're going to apply and ask for a priority review or a faster review, you're going to want to make sure everything's in order, you've done all your monitoring, and the paperwork's in place to be able to do well in such inspections. And then also to consider the implications for coverage and reimbursement of a product. You know, there's always this tension between getting a product through the FDA quickly and sort of with the least burdensome amount of data that's necessary to get through the FDA, but that may not satisfy requirements for reimbursement of a product, so those are going to have to be balanced out by an applicant.

Kellie Combs: Thanks for tuning into our podcast, Non-binding Guidance, which is brought to you by our attorneys in the life sciences regulatory and compliance practice at Ropes & Gray. For more information about our practice or other topics of interest to life sciences companies, please visit our FDA regulatory and life sciences practice pages at www.ropesgray.com. You can also subscribe to Non-binding Guidance and other RopesTalk podcasts in Ropes & Gray's podcast newsroom or on our website by searching for Ropes & Gray podcasts in Apple Podcasts, Google Podcasts or on Spotify. Thanks again for listening.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Authors
Similar Articles
Relevancy Powered by MondaqAI
 
In association with
Related Topics
 
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
 
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
Mondaq on Twitter
 
Mondaq Free Registration
Gain access to Mondaq global archive of over 375,000 articles covering 200 countries with a personalised News Alert and automatic login on this device.
Mondaq News Alert (some suggested topics and region)
Select Topics
Registration (please scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.

Disclaimer

The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.

General

Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions