Medical Device Monday: Gore Cardioform Septal Occluder Supplement

Back in 2006, FDA approved a medical device called the GORE®CARDIOFORM Septal Occluder (Yes, Medical Device Monday typically covers new devices but just bear with us for a second). The GORE®CARDIOFORM Septal Occluder is a heart implant used to close a hole in the heart called patent foramen ovale, or PFO. Recently, the creators of GORE®CARDIOFORM applied to have a supplement to the device approved by the FDA, and we are here this week to tell you that that supplement has been approved. Before we get into what exactly the supplement is, let’s dive a little deeper into what the device does.

First off, there are two different kinds of holes you can have in your heart. One is called an atrial septal defect (ASD), and the other is a patent foramen ovale (PFO). ASD is a congenital heart defect defined by the failure of the septal tissue formation between the right atrium and the left atrium, which are the two upper chambers of the heart. While ASD can occur before birth, PFO can only occur after birth, when the foramen ovale fails to close. This naturally-occurring hole allows blood to circumvent the fetal lungs, which are non-functional until birth. When a baby is born and takes its first breath, the foramen ovale is supposed to close, and within a few months seals completely. However, should it fail to close the the patient is said to have PFO. This occurs in about 25 percent of the normal population with no adverse health effects. In fact, most people with the condition don’t even know they have it! PFO causes small amounts of blood to leak from the right side to the left side of the heart, which can create problems especially if the blood contains a blood clot that could lead to cryptogenic stroke.

To help combat this, the GORE®CARDIOFORM Septal Occluder device consists of an occluder which is implanted in the heart with the help of a delivery catheter (a small tube). The occluder is made of self-expanding Nitinol wire frame, which is covered with a thin ePTFE membrane. The ePTFE is coated with a hydrophilic substance to enable echocardiographic imaging of the occluder and surrounding heart tissue during implantation. The occluder is shaped as two discs connected in the center that makes contact with the walls on both sides of the PFO to stop the leakage of blood between the atria. The occluder can be compacted to a small size to allow it to pass through the delivery catheter to be implanted within the heart. The occluder is delivered at the PFO site using conventional catheter delivery techniques wherein the catheter is inserted through the vein to reach the heart. At the site, the occluder expands where one disc covers the right and the other disc covers the left side of the PFO. Once implanted, the occluder helps block shunting of the blood from the right to the left atrium. The supplement that has been recently approved by FDA was the expansion of the indications to include closure of the patent foramen ovale to reduce another type of stroke, recurrent ischemic stroke. Ischemic strokes occur as a result of a blockage within a blood vessel that supplies blood to the brain, and can lead to extensive brain damage.



(Picture from goremedical.com)

The GORE®CARDIOFORM Septal Occluder is indicated for use in adult patients who have had a previous episode of cryptogenic stroke and are on blood-thinners (such as aspirin) to prevent another stroke. In a multinational clinical study published in the New England Journal of Medicine, there was a 77% reduction in recurrent stroke for cryptogenic stroke patients treated with the GORE CARDIOFORM Septal Occluder plus blood-thinning medication, as compared to blood-thinning medication alone. 

This is a great example of a device that is able to expand its indications after new clinical data surfaces. Congrats to Gore Medical and to those patients who avoid devastating brain damage thanks to this technology!

Click here for a video from the company website explaining the placement of the device.


Suggested Reading:

  1. Approval Letter

  2. Summary of safety and effectiveness

  3. Company website

  4. FDA news release



Medical Device Monday: Artificial Intelligence to Detect Vision Loss in Diabetic Adults

Today’s science and technology is truly beginning to look like a SciFi movie: robots and medical devices with artificial intelligence performing tests and tasks to help make new discoveries and form conclusions that we might not be able to. We— as humans— can only do so much, but with the help of new, smarter medical devices, we can make more discoveries, improve diagnoses, and enhance a patient's quality of life. Artificial intelligence (AI) is a technology that uses algorithms and software to interpret complex data without human help, and is something that has definitely been on the medical horizon for a while. Thanks to the Breakthrough Devices Pathway (defined in a Wednesday Wisdom earlier this month), a new medical device has just been granted by the FDA that will help millions of patients.

IDx-DR is a device recently granted via the de novo pathway, and is geared towards adults with diabetes who run the risk of vision loss. There are more than 30 million adults living with diabetes in the US today, and one of the risks that comes with diabetes is vision loss, or diabetic retinopathy. Diabetic retinopathy is the most common cause of vision loss among adults with diabetes, and occurs when high blood sugar levels lead to swelling and leakage of blood vessels in the retina. There are two stages of diabetic retinopathy: the initial stage is called the Non-Proliferative Diabetic Retinopathy (NPDR) and the advanced stage is called the Proliferative Diabetic Retinopathy (PDR) which can lead to blindness. In NPDR, the tiny blood vessels weaken and can leak blood and fluid into the retina. Sometimes the blood vessels close and blood cannot reach the macula; these events lead to a blurry vision. In PDR, damaged vessels eventually close off leading to the growth of new, abnormal blood vessels in the retina. These new blood vessels can also be leaky...leading to an imbalance of the normal flow of fluid out of the eye...leading to pressure build up and eventual optic nerve damage. Additionally, the scar tissue stimulated by the growth of new blood vessels may lead to retinal detachment. IDx-DR is the first medical device to use artificial intelligence to detect higher levels of retinopathy in diabetic adults, and is a medical device developed to discover and detect these indicators to prevent vision loss.

Early detection of diabetic retinopathy is very critical in preventing vision loss, and this new medical device is one that works to make early detection more common, ultimately cutting down the percentage of diabetic adults that lose vision from diabetic retinopathy. The current mode of diagnosis involves a visit to the ophthalmologist who will either do a fluorescein angiography— where a yellow dye is injected to see what is happening with the retina— or an Optical Coherence Tomography (OCT) to measure the thickness of the retina.

Compared to these modes of diagnosis, IDx-DR promises to provide an immediate, reliable assessment for diabetic retinopathy which can be used even at a primary care physician’s office. One of the great things about it is you don’t have to be a rocket scientist to use it! It is designed to be user-friendly, and can be administered by trained novice operators who have no prior experience with ocular imaging.

Don’t believe me? Let’s figure out how this thing actually works...

Using a Topcon NW400 camera, the operator captures images of the retina. The retinal images are then uploaded onto a computer where the IDx-DR software is installed. The IDx-DR software then analyzes retinal images using algorithm to detect signs of retinopathy.  In less than a minute, the operator will receive a results report with one of the three outputs:

a.       Exam quality is insufficient if the images are of low quality

b.      Negative for more than mild diabetic retinopathy. Retest in 12 months.

c.       More than mild diabetic retinopathy detected. Refer to an eye care professional.

In a 2017 clinical study, IDx-DR was tested on 900 diabetic patients across 10 sites in the US. IDx-DR was successful in detecting mild diabetic retinopathy with 87% sensitivity and 90% specificity. That’s pretty awesome! Unfortunately, IDx-DR cannot be used on patients who already have vision loss, blurred vision, or floaters. It is also contraindicated in patients diagnosed with other eye issues, like macular edema, severe non-proliferative retinopathy, proliferative retinopathy, radiation retinopathy, or retinal vein occlusion. Finally, IDx-DR can be used to only detect diabetic retinopathy and not any other ophthalmic diseases.

With an estimated 24,000 people who go blind from diabetic retinopathy each year due to lack of screening, IDx-DR promises to be a novel device in managing diabetic retinopathy. The benefit of this device far outweighs the risk and we're excited to see it come to market!  

 Image from https://www.retinamd.com/

Image from https://www.retinamd.com/

FDA Friday - Device Evaluation Intern Program

Our #FDAFriday series has focused on some of the various roles at FDA from former FDA employees. Well, what if we told you FDA is looking to hire you!?


In one of AcKnowledge RS’ first blog posts (woah, I just checked and that was almost 2 years ago!), I talked about how I got into Regulatory Affairs (RA). In that post I discussed some options and suggestions for people who might be trying to do the same. To recap, there are several different ways you can break into RA, namely by checking local and national resources, by taking regulatory courses offered online or at certain universities, and most importantly, networking! But FDA is taking it one step further and making it even easier to cut your teeth on one of the coolest career paths out there. 

Many device companies offer “hands-on” internships during the summer, which is a great opportunity for college students on summer break and recent graduates who are looking for some summer experience. The Office of Device Evaluation (ODE) at FDA just announced one such internship program. ODE, at the Center for Devices and Radiological Health (CDRH), is the part of the FDA that is responsible for the review and regulation of new medical devices before they are introduced into the marketplace. 

The Device Evaluation Intern Program is the internship program that allows college-aged students to receive some experience in the field, and is offered year-round. When it comes down to the end, the program settles on 4-5 selected interns to participate in the program. The FDA also has a program that is designed specifically and primarily for students and recent graduates, and is called the Federal Pathways Program. Any and all applicants are encouraged to apply through the usajobs website (see links below).

ODE describes the internship opportunity as follows:
“Our Intern Program can be a challenging and rewarding experience for individuals interested in pursuing careers in the fields of science, engineering, and/or medicine. You will be given the opportunity to test your educational interests in a practical work environment, gain entry level professional "real work" experience, work alongside some the Agency's top healthcare authorities, establish professional contacts and most importantly, have a learning experience of a lifetime.”

FDA writes that the duties and responsibilities of the intern include:

  • Obtain and review technical literature or data to determine the safety, efficacy, and degree of risk to the public health of medical devices;
  • Perform administrative duties associated with device submissions, write minutes of technical and administrative discussions held between division personnel, industry, and management;
  • Assist senior reviewers in obtaining and reviewing technical data and material related to medical device submissions (510(k)s, IDEs, and PMAs);
  • Perform literature searches for senior scientists and prepare summaries;
  • Assist in preparing correspondence regarding informal inquiries about various types of medical devices.

The intern will get opportunities to participate in meetings, lunch seminars, and intern get-togethers. What a great opportunity to work at FDA!

So, how do you apply to the program? Apply through the http://www.usajobs.gov/ website. Your application should include a cover letter with a summary of your interests in the medical device area. You can mention all the cool stuff about medical devices you’ve learned over here on the AcKnowledge RS blog!

Wednesday Wisdom: Breakthrough Devices Program


#WednesdayWisdom here at the AcKnowledge RS blog space consists of changes in FDA regulations, updated guidance, new programs, and regulatory considerations that we find interesting. The regulatory world is constantly changing with new medical technology and different questions surrounding device safety and effectiveness. Let us know if you have any regulatory questions that you'd like addressed at info@acknowledge-rs.com.

Last week, we mentioned a program called the Breakthrough Devices Program in our blog post about a quick, non-invasive test that could help diagnose the degree of a brain injury. The post from Monday has generated many emails and questions regarding the Breakthrough Devices Program, and today, we are here to settle the seas and answer some questions in order to better educate our readers about what this program really is!

The Breakthrough Devices Program— established under the 21st Century Cures Act in 2016— is a program in which devices with innovative and breakthrough technologies for life-threatening and irreversibly debilitating diseases are approved. These devices that get approved through this program are great for two different reasons: they either offer solutions for diseases for which no approved or cleared treatments exist, or they provide significant advantages over treatments that are already pre-existing. The Breakthrough Devices Program is an expansion of the Expedited Access Pathways (EAP), a program for devices that are subject to Premarket Approval applications (PMAs), 510(k) premarket notifications, or De Novo designation. The Breakthrough Devices Program is intended to help patients get timely access to breakthrough technologies by reducing the time and money to develop and market these devices. In that sense, this program is intended to help both the patients and the device manufacturers. Just think of the program as a catalyst of sorts, or— in the most basic sense— like getting upgraded to business class on a long flight; the devices that get approved/cleared/granted through the program get extra attention and may receive a decision quickly in order to get them to the patients in a more timely matter.

The program is a non-User Fee (this means it’s free!), voluntary program in which the device sponsor can contact FDA during early phases of the device development to help with a device study plan. The Breakthrough Devices program helps sponsor with an interactive, priority review involving senior management and a case manager. The early interaction helps the sponsor develop an efficient study plan to evaluate devices with complex technologies.

For a device to be considered “breakthrough”, the following criteria should be met:

  1. It should provide a more effective treatment or diagnosis for a life-threatening or irreversibly debilitating human disease or conditions.


The device should meet at least one of the following four conditions:

  1. It should represent a breakthrough technology;

  2. There should be no approved or cleared alternatives existing for the device;

  3. The device should offer advantages over existing devices including the potential to reduce or eliminate the need for hospitalization, improve patient’s quality of life, facilitate patients' ability to manage self-care or establish long-term clinical efficiencies; or

  4. The availability of which is in the best interest of patients.

Sponsors intending to use this program should submit a Pre-Submission for an EAP designation. Unless there is insufficient information, FDA grants EAP designation within 30 days of receipt of a request. The EAP designation, however, can be revoked if the device no longer meets the criteria outlined by the EAP guidance document or if any untrue or false documents were submitted in support of the request. Also, just because you think your device is breakthrough doesn't always make it so. Keep in mind that FDA might not agree with your request, though that shouldn't be a reason to despair! We hear this has happened to a few companies who intend to submit a traditional premarket notification. (Remember, the whole premise behind the 510(k) program is 'demonstrating substantial equivalence' to a device that's already on the market. This might be hard to reconcile with the criteria listed above.) 

FDA grants the EAP designation based on benefit-risk determinations. If the device provides considerable benefit to patients with a life-threatening disease when no alternative treatments are available, then FDA grants the EAP designation if adequate post market controls are in place.

Ever since the establishment of the program, 54 devices have been granted breakthrough status through the Breakthrough Devices Program. Many of these devices have progressed to become extremely effective mechanisms that are highly exalted. One such device that has attained much success is the Orion Cortical Visual Prosthesis System from Second Sight Medical Products Inc., a brain implant that is targeted towards blind people who have damage to their optic nerve. The device mimics light perception and transmits signals to an implant that is situated in the patient’s visual cortex, a truly remarkable development in the medical and optic world.  

Overall, the Breakthrough Devices Program, as developed by the FDA, promises to have the patient’s interest as the foremost concern, without compromising on the safety and effectiveness. While it might not be a good fit for all devices (i.e. if your device isn't breakthrough, or you're all ready to submit and the review of your request may delay your submission), we think this program is a potential win/win/win situation for FDA, industry, and patients!

Further Reading:

  1. Draft Guidance for Industry and FDA Staff

  2. Medical Device Monday from April 2, 2018

  3. Example of Data Development Plan

Med Device Monday: Diagnostic for Detection of Brain Trauma

 Image from thepinetree.net

Image from thepinetree.net

Every once in a while, a "breakthrough" medical device promises to address unmet medical needs through its innovative technology. Such devices are reviewed by the FDA under their Breakthrough Devices Program, which allows for expedited development and release of the devices into the market. One such promising in vitro diagnostic device is for detection of mild traumatic brain injury (mTBI)—commonly known as concussion. The Banyan BTI (Brain Trauma indicator) is a biomarker-based, in vitro diagnostic blood test developed by Banyan Biomarkers, Inc. That's right! A blood test for brain trauma. Truly, we are living in the future. 

Traumatic brain injury (TBI) is an injury to the brain following a violent blow to the head. Accidents, sport-related concussions, and falls can all cause TBI. In turn, TBI can be classified as either Mild and Severe. Mild TBI, or mTBI, causes loss of consciousness for less than 30 minutes, resulting in cognitive dysfunctions such as memory loss, attention deficits, and mood swings. It is often missed at the time of initial injury. Severe TBI, on the other hand, causes loss of consciousness for more than 30 minutes. This is due to penetrating skull injury which can result in severe cognitive impairment and even a comatose state for the patient. According to the Centers for Disease Control and Prevention (CDC), in 2013 TBI resulted in approximately 2.5 million emergency visits and 282,000 hospitalizations out of which 94.5 percent of TBIs are mTBIs or concussions.

Banyan BTI detects the presence of two brain-specific biomarkers—UCH-L1 (Ubiquitin Carboxy-terminal Hydrolase-L1) and GFAP (Glial Fibrillary Acidic Protein)—which are quickly released into the blood following a concussion. Measuring these protein levels within 12 hours of a head injury can help identify intracranial lesions following an incident.

The current mode for detecting brain tissue damage is to use a neurological scale, called the 15-point Glasgow Coma Scale, followed by a computed tomography or CT scan of the head. The current methodology is defective in the sense that over 90% of patients with mild TBI have a negative CT scan. Moreover, the CT scan has the disadvantage of considerable radiation exposure to patients. Availability of a blood test for mTBI/concussion will likely reduce the amount of CT scans done—saving essential dollars for our health care system.

According to a multi-center, clinical study of 1,947 individual blood samples from adults with suspected mTBI or concussion, and compared with CT scan results, Banyan BTI was able to predict the presence of intracranial lesions with an accuracy of 97.5 percent. Banyan BTI was cleared by FDA via the de novo pathway, and it promises to be the first objective blood test that will help clinicians rule out the need for unnecessary CT scans in persons with mTBI.

These are exactly the types of breakthrough devices that FDA seeks to get to market: it's less invasive and risky for patients, and provides quick results at a lower cost. What's not to like? 


Further Reading: