FDA Friday: New Guidance for Humanitarian Use Devices

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Roughly one out of every 10 Americans lives with at least one of more than 7,000 rare diseases. As explained at rarediseaseday.org, a disease or disorder is defined as rare in the USA when it affects fewer than 200,000 Americans at any given time. These conditions often have genetic origins whilst others are the result of infections (bacterial or viral), allergies and environmental causes, or are degenerative and proliferative. Tragically, half of those affected by rare diseases are children.


FDA came up with a program after recognizing the need for a more streamlined process of approval for different types of medical devices that could potentially serve as a cure or relief to a rare disease. This program was formed in 1990, and is called the Humanitarian Device Exemption (HDE) Program, which creates new regulatory pathways for devices and products that are intended for rare diseases. Due to the fact that these rare diseases are so infrequent or uncommon, developers are unable to gather enough clinical evidence to support and meet the normal FDA standard of assurance and safety, which is why the HDE Program was created.

 

The devices which are submitted to the HDE Program for approval are called Humanitarian Use Devices (HUDs), and are defined as “medical devices that are intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year” (Source). Each of the HUDs are submitted with an HDE, the marketing application that is exempt from the effectiveness requirements that pertain to normal applications. FDA may grant an HDE if the device meets all of the requirements, which are as follows:

 

  1. The device will not expose any patient to a high level of danger and/or illness, and the benefit from use of the device outweighs any risk that may come from using the device.

  2. The device is available only through the HDE, and there are no other similar devices that have already achieved approval that could potentially treat or diagnose such disease or condition.

  3. The device is designed to diagnose or treat a rare disease or condition, where “rare” means that not more than 8,000 individuals in the U.S. are affected each year.

 

The draft guidance document titled “Humanitarian Device Exemption (HDE) Program” was released by FDA this week in order to answer questions about the HDE program. FDA has provided this information in the hopes that sharing the information will help bring awareness to more manufacturers and companies, and therefore expand the number of medical devices that are geared towards helping rare diseases or conditions.  

Additional Reading:

Medical Device Monday: Cala ONE's Essential Tremor Device

What happens when experts in the fields of neuroscience, consumer electronics, and data science come together? While your first thought is likely, "the most epic party ever," the correct answer is: they develop a cutting-edge neuromodulation device. Cala ONE, by Cala Health, is a non-invasive, neuroperipheral therapy device that aims to provide transient relief of hand tremors in adults with essential tremor. The device is another success story out of the de novo program at FDA, and was granted marketing authorization this past April (2018). To understand the impact of the device, let’s talk a little more about essential tremors.

Essential tremor (ET), also once known as familial tremor, is a common movement disorder affecting almost 10 million Americans, and millions more worldwide. The condition is often confused with Parkinson’s, and causes rhythmic trembling of the limbs, head, and voice. The constant shaking makes it difficult to perform even the most basic daily activities like eating, drinking, and writing. Although the exact causes and mechanisms of the disorder are unknown, it is believed that they are mostly inherited, and are caused by tremulous activity within a central tremor neural network.

Current treatment options for tremors centralize almost entirely around medications. Some of these medications include beta-blockers and anti-seizure drugs that often have undesirable side effects. In cases where medications fail, alternative treatments like Botox injections or invasive surgical options are used, which can also be just as dangerous as the side effects that come with medication. Cala ONE promises to be a non-invasive, non-pharmacological targeted nerve stimulator for symptomatic relief of hand tremors. The device, which looks quite similar to a fitness tracker or smart watch, delivers patterned electrical stimulation to the median and radial nerves— part of the peripheral nervous system— in the wrist, through the skin.  Two randomized controlled studies, one being an in-clinic study that included 77 participants, and the other an at-home study that included an additional 61 participants, showed marked improvement in those that received treatment stimulation when compared to those that received sham stimulation. Cala ONE is another device in the ever-expanding area of personalized medicine wherein a physician can measure an individual’s tremor using on-board sensors and tailor the treatment according to the patient.

 

 Image from mobilehealthnews.com

 

This new device aims to benefit people with ET who might not be able to do things that were once second nature to them. Our abilities to hold someone’s hand, throw a dog a ball, enjoy a home-cooked meal, and write our name are often taken for granted. Thanks to neuroscience, consumer electronics, and data science experts coming together (and likely having an epic party of the minds), this device stands to benefit many people who have been unable to take those actions for granted.

 

Suggested Reading:

  1. FDA de novo Classification Order

  2. Cala Health Website

  3. More information about Essential Tremor

 

FDA Friday: FDA's New Challenge to Help Combat Opioid Use Disorder

FDA Friday: FDA New Challenge to Help Combat Opioid Use Disorder

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The Food and Drug Administration has recently launched a challenge to initiate development of medical devices to help combat against the opioid crisis. FDA is looking to medical device manufacturers to help protect and promote the public health by finding new ways prevent and treat opioid use disorder.

Many people are used to hearing “substance abuse” or “substance dependence,” but those terms have become outdated. Current terminology states that “substance use disorders” can be evaluated as mild, moderate or severe. Substance use disorder is defined by the repeated use of drugs and/or alcohol that ultimately results in significant impairment in many areas. The challenge that FDA is promoting focuses entirely on opioid use disorder, a very serious health condition that can have devastating outcomes. Opioids reduce pain perception and are a very effective pharmaceutical solution to certain medical conditions, however, when misused, can cause serious health effects and may lead to addiction. The lurking end to those who tamper with and misuse opioids is, unfortunately, overdose, which has become an increasing occurrence over the past 18 years. It is clear why FDA has focused on this disorder, and expressed a need for medical devices that can help put an end to the countless deaths that come from opioid misuse.

This innovation challenge exemplifies the commitment of FDA to confront medical epidemics, as well as provides developers with the opportunity to work with FDA directly. Some examples of medical devices that are great candidates include diagnostics, devices that prevent diversion of prescribed opioids, withdrawal treatment devices, and pain therapies that exclude opioids. Applications for this challenge will be accepted from June 1 through September 30, 2018. Those who are accepted into the challenge will have direct communication with FDA review divisions throughout the development of the proposed product. Furthermore, the devices that meet the criteria will be granted Breakthrough Device designation. The proposals that are submitted will be evaluated based on the feasibility, public health impact, and novelty of the concept. The number of proposals that will be selected will be based off of the quality of the proposals that are received. The “winning” devices chosen to participate in the challenge will be announced in November 2018. And hey, when industry and FDA come together to battle opioid use disorder, it’s a true win for America!

Prior to the selection of devices and closure of the competition, FDA will host a webinar on July 25, 2018, where developers can ask questions about the challenge. FDA remains committed to addressing the opioid crisis, and this challenge is just one component of their work to reduce the increasing numbers of opioid users around the world.

 

Further Reading:

  1. Challenge Website

  2. Webinar Website and Information

 

 

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.

 

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(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/