FDA

Med Device Monday: BONEBRIDGE by Med-El

Hearing loss is the third most common health problem in the U.S after heart disease and arthritis. It is estimated that about 48 million Americans have some form of hearing loss, often caused by illness, genetics, or other ear-damaging elements that come with a modern lifestyle (e.g. sporting events, airplanes, concerts, and working with heavy machinery). FDA recently granted a de novo request for the BONEBRIDGE device, manufactured by Austrian company, Med-El. BONEBRIDGE is an active bone conduction implant system, and is designed for individuals 12 years and older who have conductive hearing loss, mixed hearing loss, or single-sided deafness.

To understand who should use this device, we need to understand a little more about the types of hearing loss. Hearing loss can be categorized into 4 categories:

  • Conductive: Any problem in the outer or middle ear that prevents sound from being conducted properly.

  • Sensorineural: Hearing loss that results from missing or damaged sensory cells (hair cells) in the cochlea and is usually permanent.

  • Mixed: As the name suggests— is a combination of conductive and sensorineural hearing loss, indicating damage in both the outer or middle ear, and the inner ear.

  • Neural: Neural hearing loss results from the lack of or damage to the auditory nerve, which is a bundle of fibers that carries auditory sensory information from the cochlea to the brain.


Traditional cochlear implants help patients who have sensorineural hearing loss as they replace the functional components of the inner ear (read more about cochlear implants on our blog from May 2016)! Alternatively, BONEBRIDGE is indicated for conductive or mixed hearing loss, which means sound cannot take the natural route through the outer and middle ear to the inner ear. This makes it difficult for the hearing loss sufferer to hear soft sounds and can also lead to the muffling of louder sounds.

 Image from www.medel.com/us/bonebridge

Image from www.medel.com/us/bonebridge


BONEBRIDGE transmits sound waves via bone conduction directly to the inner ear, where they are processed as natural sound. The device consists of two components: an externally worn audio processor (called SAMBA), and a surgically-inserted bone conduction implant (called the BCI 601) which lies directly beneath the skin. The audio processor is held directly above the implant using magnetic forces.

Now, let’s get into the specifics of how this device works! Initially, the microphones of the audio processor pick up the sound waves. Then, the audio processor converts those sound waves into electrical signals, which are then transmitted through the skin to the implant. The implant, which is fixed in the temporal bone, converts these electrical signals into mechanical vibrations which are transmitted to the skull. The bone then conducts these vibrations to the inner ear. Signal transmission to the inner ear via bone conduction bypasses the outer and the middle ear, solving the complication of sound’s inability to pass through the natural route that comes with conductive and mixed hearing loss. The inner ear then processes these mechanical vibrations in a way that is similar to the way natural hearing is processed, and transmits nerve signals to the auditory nerve in the brain.

The audio processor is equipped with adaptive directional microphones, which adapts to different environments and individual usage. One of the really cool things about the audio processor (not that the device isn’t already super cool) is that it automatically identifies and minimizes noise interference in situations where there is loud background noise, which can become overwhelming to people who aren’t used to those background noises. The audio processor also comes with a remote control that has wireless connectivity capabilities. Using this remote control, the users can select different programs that have various settings depending on the user’s current environment or activity.

FDA classified BONEBRIDGE under product code PFO as a Class II device with special controls. These special controls include:

1.       Clinical performance testing

2.       Non-clinical performance testing (includes impact testing, mechanical Integrity testing, etc.)

3.       Biocompatibility testing

4.       Sterility of the patient-contacting components of the device

5.       Shelf life of the device

6.       Wireless compatibility, electromagnetic compatibility, and electrical safety

7.       Software verification, validation, and hazard analysis

8.       Labeling

 

We’re so excited to see medical technology like this enter the US market!

Additional Reading:

1.       FDA Classification Order

2.       Video explaining how the BONEBRIDGE works

3.       More info about BONEBRIDGE

4.       More info about the de novo process HERE and HERE

FDA Friday: Updates to our Previous De Novo Pathway Blog

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A little over two years ago, in one of our earlier blog posts, we discussed the de novo pathway. Since then, while the fundamentals of the program have remained the same, several changes have occurred to this pathway in terms of user fees and review time. We’d like to bring you up to speed on some of the changes in this blog post.

Briefly, the de novo pathway (as mentioned in our previous blog post) is an alternate pathway added through the Food and Drug Administration Modernization Act of 1997 (FDAMA). This pathway was added in order to classify novel, low- to moderate-risk Class I and Class II medical devices that did not have an acceptable predicate device (in order to establish substantial equivalence via the 510(k) pathway), and had not already been classified as Class III (“high-risk” devices).

There are still two routes for a de novo classification:

1.       Submitting a de novo request to the FDA after an NSE determination in response to a 510(k) submission.

or,

2.        If there is no legally marketed device upon which to base a determination of substantial equivalence, the sponsor may submit a de novo request without first submitting a 510(k) and receiving an NSE determination.

 

Such devices cleared through the de novo pathway may be used as predicates for future 510(k) submissions. Though not required, FDA strongly recommends a Pre-Submission in order to obtain early feedback from FDA, saving the submitting company both time and money. A Pre-Submission will not only help sponsors obtain feedback on whether a device may be eligible for the  de novo classification process, but also feedback on any on non-clinical and/or clinical data that will likely be necessary to support the de novo request.

In terms of the submittal, the de novo application should be submitted as an e-copy to the appropriate Document Control Center in CDRH or CBER. FDA’s goal is make a decision on the de novo request in 150 days. Since 2010, FDA has been releasing summaries of the devices cleared through the de novo process which will help sponsors that may wish to use the device as a predicate for future 510(k) submissions. Starting on October 1, 2017, changes were made to the user fees that are as follows: FDA now charges a fee for review of the de novo application unless you qualify for one of the exceptions:

1.        The device being submitted is a device intended solely for a pediatric population

or,

2.       Any application from a state or federal government entity

 

In 2017, FDA also released guidance documents on the de novo Classification Process and User Fees and Refunds for de novo Classification Requests.  De novo may be a faster pathway for you to get your novel, low- to moderate- risk devices to the market. Ask your regulatory consultant if a de novo is right for you!

 

Additional Reading (Guidance Documents):

1.        Our Previous Blog about De Novos

2.        De Novo Classification Process

3.       User Fees and Refunds for De Novo Classification Requests

4.       FDA and Industry Actions on De Novo Classification Requests: Effect on FDA Review Clock and Goals

5.       Acceptance Review for De Novo Classification Requests

Med Device Monday: Ellipsys Vascular Access System and the everlinQ endoAVF System

On June 22, 2018, FDA issued a release that permitted marketing of two different catheter-based devices that are designed to connect veins and arteries in patients with chronic kidney disease. One of these devices is called the Ellipsys Vascular Access System, and is a product from Avenu Medical. The other device is the everlinQ endoAVF System from TVA Medical. Now, we’re not here to do a side-by-side comparison of both devices. However, we do want to talk about this pretty innovative technology and discuss why it is uncommon for two devices to get de novo granting at the same time.

These minimally-invasive devices create a percutaneous arteriovenous (AV) fistula for hemodialysis access. "Huh?" Yeah, that's what we said too, until we read a little more about this procedure and device. Let's break it down a little, shall we?


The National Institutes of Health reports that more than 661,000 Americans have kidney failure, and two-thirds of that group of people are on hemodialysis. Hemodialysis is a kidney dialysis and blood-cleaning process, where blood is put through a filter outside of the body, cleaned, and then returned to the body. Dialysis is necessary and life-saving in many cases for patients with kidney diseases. Surgeons can create AV fistulas which allow blood to flow from the artery directly into the vein, increasing the blood pressure and amount of blood flow through the vein. This increased flow and pressure causes the veins (typically in the arm) to enlarge slightly. In turn, this enlargement provides the amount of blood flow necessary to ensure an adequate hemodialysis treatment. AV fistulas are the preferred vascular access for long-term dialysis because they last longer than any other dialysis access types, are less prone to infection and clotting, and can be relied upon for predictable performance. Unfortunately, AV fistulas can take several months to heal in order to become usable for hemodialysis. This process has been around for a while, and the procedure hasn’t changed in 50 years.

 Ellipsys Catheter Device (Image from www.avenumedical.com/ellipsys)

Ellipsys Catheter Device (Image from www.avenumedical.com/ellipsys)

Both the Ellipsys Vascular Access System and the everlinQ endoAVF System takes a common surgical procedure and simplifies it, cutting actual procedure time down to 30 minutes or less, and requiring only the use of regional or local anesthetic. The Ellipsys Vascular Access System uses an intravascular approach and occurs in the upper forearm, where an outer access cannula, guidewire, and vessel capture construct all combine to create a connection between the vein and artery. A low-power thermal energy is then used to cut the walls of the vessels, and then fuse the tissue together, creating a cross-connection between the adjacent channels without leaving any kind of foreign material in the AV fistula. No stitches, no sutures, no implant.

For people interested in how this is done, here is the step-by-step procedure:

  1. Ultrasound imaging is used to guide catheter to access perforating vein and puncture adjacent radial artery

  2. Guidewire is placed into radial artery

  3. Sheath is inserted over guidewire and into radial artery

  4. Ellipsys catheter is inserted

  5. Catheter is positioned to capture both artery and vein walls

  6. Ellipsys catheter is activated

  7. Catheter is extracted

  8. AV Fistula created

 everlinQ endoAVF Catheter (Image from www.tvamedical.com)

everlinQ endoAVF Catheter (Image from www.tvamedical.com)

While the Ellipsys device uses one catheter in the procedure, the everlinQ System uses two catheters. The two catheters are magnetic, and attract and lock together once they are aligned in the arm arteries (more specifically, the venous everlinQ catheter in the ulnar vein, and arterial everlinQ catheter in the ulnar artery). Once the everlinQ catheters are locked together, an electrode is deployed and radiofrequency energy is delivered to created channel between artery and vein. 

For people interested in how this procedure is done using the everlinQ System, here is the step-by-step procedure:

  1. Two thin flexible magnetic catheters are inserted into artery and vein in the arm through a small incision

  2. Fistula is confirmed with arteriogram to show arterial blood is flowing to low pressure venous system, creating multiple options for cannulation

  3. Venous catheter, which contains electrode, delivers a burst of RF energy to create connection between artery and vein. Catheters are removed

  4. When placed in proximity, magnets in each catheter attract to each other, pulling vessels together. After confirming alignment, RF electrode is deployed

Both of these de novo-reviewed devices have undergone studies, and intense pre-clinical and clinical testing.If you geek-out on regulatory stuff like we do, you might have noticed that these two devices got de novo granting at the same time. In FDA’s guidance document De Novo Classification Process (Evaluation of Automatic Class III Designation), FDA states: “We do not anticipate that De Novo requests for the same device type will frequently be under review concurrently. However, in cases where a De Novo request is granted while another device of the same type is under review in a separate De Novo request, after the first De Novo request is granted, FDA intends to notify the submitter of the other De Novo request still under review that a predicate has been established and that the De Novo request still under review will be declined. The submitter of the declined De Novo request may leverage all information in the De Novo request by incorporating it by reference in a new submission but will still be required to demonstrate substantial equivalence in a subsequent 510(k), including conformity with the newly established special controls for the device type (if Class II).” So it looks like FDA did a solid for these companies and granted both de novos for this new product code (PQK) at the same time (June 22, 2018). Based on the de novo classification orders public on the FDA website, the Ellipsys Vascular Access System (DEN170004) and the everlinQ endoAVF System (DEN160006) were submitted at very different times. It’s nice to see that no one had to turn their de novo into a 510(k) after the other company got “first-to-market” advantage! This way, everyone wins, especially patients who want to get the best treatment possible when they talk to their doctors about this device!

 

Further Reading:

  1. FDA News Release on Ellipsys Device and everlinQ System Device

  2. Ellipsys Device Information on Avenu Website

  3. Ellipsys Device Brochure

  4. WATCH: How the Ellipsys Device Works

  5. everlinQ endoAVF System Information on TVA Medical Website

  6. WATCH: How the everlinQ System Works


 

FDA Friday: FDA's Looking for Sites to Participate in their Experiential Learning Program

Calling all medical device companies, academics, contract manufacturers, incubators, tech accelerators, health insurers, third party test labs, and healthcare facilities! FDA wants to come visit YOU! 
[And not to worry, they won't throw in a free "inspection" while they're there.]

biology-clinic-doctor-4154.jpg


The Center for Devices and Radiological Health (CDRH) is offering an innovative learning opportunity for new and experienced FDA review staff. The Experiential Learning Program (ELP) is intended to provide a formal training mechanism for regulatory review staff to visit research, clinical, manufacturing, and healthcare facilities to observe how medical devices are designed, developed, and utilized. The ELP is intended to provide CDRH staff with an opportunity to understand the policies, laboratory and manufacturing practices, and the challenges addressing patient perspective/input, quality system management, and other challenges that impact the device development life cycle.

It's always exciting for FDA reviewers to leave their offices in Silver Spring to go out and see what you're doing! This program is a collaborative effort to enhance communication and facilitate the premarket review process. As mentioned earlier, these visits are not intended for FDA to inspect, assess, judge, or perform a regulatory function (e.g., compliance inspection), but rather, they are an opportunity to provide CDRH review staff a better understanding of the products they review, how they are developed, the voice of the patient, challenges related to quality systems development and management in the product life cycle, and how medical devices fit into the larger healthcare system. And hey, maybe it'll help some people in industry realize that FDA is made up of real flesh-and-blood humans too! We all move forward when we can learn from each other. 


Areas of Interest
Areas of Interest for visits are identified by managers at CDRH and are listed on the FDA website (see link below). The Areas of Interest will be updated quarterly, and assigned a one month submission window time-frame. If you're interested in ELP participation, you should preview the identified Areas of Interest by viewing the list. Once an Area of Interest has been determined, the Sample Site Visit Request and the Sample Site Visit Agenda templates can be utilized to make a request for participation. Currently, FDA has listed biocompatibility, combination products, clinical trials/research, device development/manufacturing/demos, digital health/software, innovation/health technology assessment, in vitro diagnostics, standards conformity testing, and quality management systems as Q1's Areas of Interest. 


Application Process Summary
Any stakeholders interested in placing a proposal in the program may submit a proposal to the program using following the steps:

  • Review the table of Training Needs displaying CDRH identified Areas of Interest.
  • Determine which Area of Interest your site would like to provide training for during a visit to your location. Each visit may last 1 or more days.
  • Utilize the Site Visit Sample Request and the Site Visit Agenda Templates to fill out your proposal for submission.
  • Complete all fields in the Site Visit Sample by first listing the Area of Interest along with its Identifier Code.
  • Proposals must be submitted to ELP Program Management within the specified dates (8/24/2018 – 9/26/2018 12:00 pm EST) in order to be considered eligible for that relevant training cycle. Proposal may be emailed to elp@fda.hhs.gov.

Further Reading:

  1. ELP Website

  2. Areas of Interest

Med Device Monday: MolecuLight i:X

FDA recently granted a hand-held imaging device (via the de novo pathway) called MolecuLight i:X. This device allows clinicians to assess, diagnose, and measure wounds by providing real-time imaging of the bacterial distribution with the guidance of fluorescence imaging. Think 'superhero vision'...but for U.S. clinicians! Wound infections are a major cost burden on the health care system and account for increased patient morbidity and prolonged hospital stays. It is estimated that approximately 5.7 million patients in the U.S. are affected with chronic wounds, which comes out to an estimated $20 billion annually.

 Image from www.moleculight.com

Image from www.moleculight.com

So, how does the device work? The MolecuLight i:X emits a specific wavelength of violet light, which interacts with wound tissue and potentially harmful bacteria present in the wound (e.g. porphyrins). The wound tissue and surrounding skin emits a green fluorescence, whereas the bacteria present in the wound emits a red fluorescence. The green and red fluorescence are captured in real-time using specialized optical components, and are then displayed on the device screen.

 Image from www.moleculight.com

Image from www.moleculight.com

The device can detect fluorescent bacteria at levels of  ≥104 colony forming units (CFU)/gram. Clinical studies indicate that MolecuLight i:X can detect common causative organisms associated with wound infections like Staphylococcus aureus/Methicillin-Resistant Staphylococcus aureus (MRSA), Beta-hemolytic Streptococci (Group B), Enterococci, and Pseudomonas aeruginosa. MolecuLight i:X can also detect wound borders and provide wound area measurements. Wound size has traditionally been determined using a wound ruler, which are particularly challenging for irregularly shaped wounds. The device can not only measure wound size and fluorescent bacteria, but it can save those images and track both size and bacteria content over time. This gives clinicians an insight as to how patients are responding to treatment, and whether or not different treatment routes need to be taken.

The device also comes with accessories such as the MolecuLight DarkDrape, which is a high density plastic sheet which can be secured to the patient ensuring appropriate lighting conditions are met when room lights cannot be turned off. Studies showed that MolecuLight i:X-guided treatment significantly increased the rate of wound healing compared with standard of care, and reduced the average closure time of chronic wounds from 200 to 22 days. It's been a while since we've taken a biostatistics class, but that sounds like a pretty favorable recovery time! 

Additional Reading

1.       MolecuLight Website

2.       Letter of Classification