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

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

Image from

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:

Med Device Monday: Nerve Stimulation for Sleep Apnea

Sleep is an essential human function, but one we tend to take for granted until it goes wrong or we're not getting enough of it—much like breathing. Breathing is of course an important part of sleep, and is an involuntary mechanism that our brains take care of even when our minds are elsewhere. But when breathing is impaired through sleep, it can mean more than just annoying snores or restlessness: sleep deprivation can be life-threatening. Sleep is essential to our well-being, supporting and enabling healthy brain-function, emotional wellbeing, memory, and overall physicality. When we sleep, our bodies repair our cells and slowly restore us—literally. Chronic sleep deprivation can lead to accidents & injury, obesity, heart disease, depression, suicide, kidney disease, diabetes, stroke, and more. All that from not catching enough Zs!

FDA recently-approved a medical device that offers an interesting new solution to this problem. Specifically, for central sleep apnea, which is when the brain neglects to properly send signals via the phrenic nerves to keep the diaphragm moving, and in turn keep air moving in and out of lungs. When a person experiences this type of sleep apnea, their heart rate increases while they cease breathing, and once the nerve function kicks back in and tells the diaphragm to move (and thus the lungs to fill), there is a period of rapid breathing—sort of like the body is catching up to get all that oxygen it missed.

Photo from

Photo from

Respicardia Inc.'s device is called Remedē® System. This nerve-stimulating device is an implant that monitors and regulates nerve activity when the patient is asleep. It can either be set to send these pulses at regular intervals, or send them only when it detects that the patient isn't breathing. Although the implant is in the patient around the clock, safeguards are in place so that it is only used when the patient is sleeping. It is also monitored by the patient's doctor. The company says that the device is implanted by a cardiologist using only local anesthesia as needed. A small generator goes under the skin, and the long thin wires are then threaded through veins near the phrenic nerves in order to stimulate them, and in turn the diaphragm. 

Try not to hold your breath while you watch this video:

This device is meant to treat moderate to severe sleep apnea of this specific type. It's important to note that this sleep apnea is different than obstructed sleep apnea, where an airway obstruction causes the disruption in breathing, and for which we have CPAP and BiPAP machines. Every type of sleep apnea is of course problematic and can be life-threatening, and it's cool to see how medicine can really narrow in on specific problems and come up with innovative solutions like these!


Further reading:

FDA info on Remede

Remede approval letter

Remede summary of safety and effectiveness


Previous Med Device Monday posts on sleep devices:

Help for restless legs

Help for insomnia

National Cybersecurity Awareness Month

Technology in medical devices! It's hardly a secret that it's one of our favorite topics around here. We talk about technology in medical devices all the time. It's also no secret that technology comes with certain risks, as with any new age of innovation. And, just like any other new age of innovation, it doesn't mean that the developments are inherently bad or should be avoided. On the contrary, technology in medicine is saving more lives. What this new frontier does imply is that users, developers, medical device manufacturers, health care providers, and everyone else in the industry and alongside it, all have an obligation to be aware of, and able to react to, new potential risks that come with the advent of increased technology. 

CRDH and FDA are aware of this too, of course. That's why they are supporting and promoting National Cybersecurity Awareness Month this October. As they say, "The FDA believes this a good time to reinforce the importance of medical device cybersecurity and the role we all play in medical device safety." Indeed! Additionally, "All medical devices carry a certain amount of risk. The FDA allows devices to be marketed when there is a reasonable assurance that the benefits to patients outweigh the risks. While the increased use of wireless technology and software in medical devices also increases the risks of potential cybersecurity threats, these same features also improve health care and increase the ability of health care providers to treat patients."

Check out the Stop.Think.Connect. Campaign, "a national public awareness campaign aimed at increasing the understanding of cyber threats and empowering the American public to be safer and more secure online. Cybersecurity is a shared responsibility. We each have to do our part to keep the Internet safe. When we all take simple steps to be safer online, it makes using the Internet a more secure experience for everyone."

Okay, so what does online security have to do with what we're interested in? Well, consider devices like two of the most recent ones we've featured here on MedDevice Monday: an app that's a medical device, and a wristband that's a medical device. Both of these medical devices require access to the internet, and interfacing on various phones, tablets, computers, or other screens. There's ample opportunity—and obligation—to practice cybersecurity best practices with devices like these. And we're only going to encounter more of them as strides continue to be made in technology. And that's a good thing! 

FDA recommends a few best practices, including, 

  • "Medical device manufacturers and health care facilities should take steps to ensure appropriate safeguards. Manufacturers are responsible for remaining vigilant about identifying risks and hazards associated with their medical devices, including risks related to cybersecurity. They are responsible for putting appropriate mitigations in place to address patient safety risks and ensure proper device performance.
  • Hospitals and health care facilities should evaluate their network security and protect their hospital systems."

You can read more about Cybersecurity Awareness Month and FDA's approach to technology at the following resources:


FDA's standing resource page on cybersecurity in digital health

FDA's fact sheet on their role in cybersecurity: myths vs. facts

Premarket management of medical device cybersecurity

Postmarket management of medical device cybersecurity





Med Device Monday: A Medical Device for Substance Use Disorders

When we think of treating substance abuse, it's typically drugs, therapies, and various rehabilitations that come to mind. But last week, FDA announced that it has approved marketing of the first medical app (yes, like the kind from the App Store) to help treat Substance Use Disorders (SUD). The device is intended to be used together with outpatient therapy, and it's not intended for use with opioid addiction or for those who are dependent only on alcohol. But still, medical treatment through a mobile app? It's hardly the first time we've said it here, but the future truly is now!

Substance Use Disorder is, in a word, addiction. The Substance Abuse and Mental Health Services Administration shows a group of disorders that fall under this title, including dependence on alcohol, cannabis, tobacco, stimulants, and hallucinogens. Note that they also make clear distinctions about the words they choose to describe these disorders, saying, "The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), no longer uses the terms substance abuse and substance dependence, rather it refers to substance use disorders, which are defined as mild, moderate, or severe to indicate the level of severity, which is determined by the number of diagnostic criteria met by an individual." They go on to say, "Substance use disorders occur when the recurrent use of alcohol and/or drugs causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. According to the DSM-5, a diagnosis of substance use disorder is based on evidence of impaired control, social impairment, risky use, and pharmacological criteria.".

Of course, most of us will unfortuantely have at least a passing familiarity with what substance dependence means and looks like. All the more reason that an accessible mobile medical device for treatment is fantastic news. 

reSET Pear Therapies addiction app
Screencaps from

Screencaps from

reSET, from Pear Therapeutics, is the name of this app, which is used on a patient's phone or tablet and monitored by their clinician via a desktop interface. It's designed to encourage and maintain abstinence from the substance the patient is dependent on. It delivers to the patient cognitive behavioral therapy (CBT) and acts as part of a larger overall plan of treatment. In fact, in clinical trials, treatment via reSET saw better outcomes than those patients who used only traditional, in-person therapy. CBT is a system of talk therapy designed to make the patient aware of negative or destructive patterns of thought and change their behavior around them. 

While this medical device is, like any medical device, not a magic bullet, it is really encouraging and exciting to see how technology can serve patients and the medical device community. This is a really promising development and I look forward to following this company and this device in the future. Check out the other devices they have on deck which have not yet been approved, by clicking here.


Further reading:

FDA's de novo approval

Pear Therapeutics press release

FDA press release: FDA permits marketing of mobile medical application for substance use disorder