Technology

Med Device Monday: The Monarch external Trigeminal Nerve Stimulation (eTNS) System: The first non-drug treatment for ADHD

Photo from prnewswire.com

Photo from prnewswire.com

A recent press release from the U.S. Food and Drug Administration (FDA) certainly caught our attention! In April, FDA permitted marketing of the first medical device to treat attention deficit hyperactivity disorder (ADHD). The device, known as the Monarch external Trigeminal Nerve Stimulation (eTNS) System, is for prescription use only and intended to be used in patients ages 7 to12 years old who are not currently taking prescription ADHD medication. The device was developed by NeuroSigma, and is the first non-drug treatment for ADHD granted marketing authorization by the FDA.

ADHD is a common disorder that often begins in childhood, with symptoms including inattentiveness, impulsiveness, and very high levels of activity. A diagnosis of ADHD requires a comprehensive evaluation by a health care professional, and for a person to receive an ADHD diagnosis the symptoms must impair the their functioning and cause them to fall behind normal development for his or her age.

The Monarch eTNS System is intended to be used at home under the supervision of a caregiver. The cell-phone sized device generates a low-level electrical pulse and connects via a wire to a small patch that adheres to a patient's forehead, just above the eyebrows. The stimulation should feel like a tingling sensation on the skin, and is administered by the caregiver when the child is asleep. The device is purported to stimulate the branches of the trigeminal nerve, which sends therapeutic signals to the parts of the brain thought to be involved in ADHD. While the exact mechanism of eTNS is not yet known, neuroimaging studies have shown that eTNS increases activity in the brain regions that are known to be important in regulating attention, emotion and behavior.

“This new device offers a safe, non-drug option for treatment of ADHD in pediatric patients through the use of mild nerve stimulation, a first of its kind,” said Carlos Peña, Ph.D., director of the Division of Neurological and Physical Medicine Devices in the FDA’s Center for Devices and Radiological Health. “Today’s action reflects our deep commitment to working with device manufacturers to advance the development of pediatric medical devices so that children have access to innovative, safe and effective medical devices that meet their unique needs.”

The FDA reviewed the Monarch eTNS System via the de novo premarket review pathway (previously blogged about HERE and HERE), a regulatory pathway for low- to moderate-risk devices of a new type. This action creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through the FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device. The main mitigation measures included biocompatibility evaluation, software validation, shelf life testing, electromagnetic compatibility and electrical safety testing. While the Classification Order has been released by FDA, we look forward to posting more info about the details of the testing that NeuroSigma provided in their de novo once the Decision Summary is made public.

Additional Reading:

1.       FDA Press Release

2.       FDA Classification Order

3.       NeuroSigma

4.       About ADHD

5.       ADHD Support Organizations

Wednesday Wisdom: Article on Regulating Software as a Medical Device (SaMD)

AcKnowledge RS’s very own Michelle Rubin-Onur wrote an article that was published this past week. Check it out on the Regulatory Affairs Professionals Society (RAPS) website HERE. In the article she discusses the rise of software as a medical device (SaMD) and how the regulatory landscape is changing for these devices. Read the abstract below, and in case you missed it, HERE is the link again to read the full article!


Regulating Software as a Medical Device in the age of Artificial Intelligence

Posted 30 May 2019 | By Michelle Rubin-Onur, PhD

“This article summarizes the current and proposed regulatory landscape for software as a medical device (SaMD) with artificial intelligence and machine learning capabilities. The author provides definitions for SaMD, categorization and testing features and how to approach and adjust regulatory pathways for SaMDs that “learn” by using real-world evidence to continuously adapt and improve and, therefore, may need to be re-submitted for a new premarket approval due to changes to the device via its adaptations. Because the regulatory system does not currently take into consideration SaMDs using Artificial Intelligence (AI) and Machine Learning (ML) to continually adapt, FDA has initiated a conversation with SaMD stakeholders to develop an appropriate regulatory pathway to accommodate AI/ML SaMD continuous adaptation.”

Med Device Monday – CureMetrix “Triage” Service cleared to Screen Mammograms for Signs of Cancer

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

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

It is estimated that one in eight women will be diagnosed with breast cancer during their lifetime. Generally, the first noticeable symptom of breast cancer is a lump that feels different from the rest of the breast tissue. In fact, more than 80% of breast cancer cases are discovered when the woman (or man…men get breast cancer too!) feels a lump. Finding breast cancer early can mean improved chances that the disease can be successfully treated. Fortunately, mammograms are often able to detect breast cancers early, and involve a simple low energy x-ray of the breast.

The use of mammograms as a screening tool for the detection of early breast cancer in otherwise healthy women is not without controversy. A mammogram that generates a false positive can cause significant stress and lead to unnecessary surgical interventions, and mammography can also generate false negatives. It is estimated that the numbers of cancers missed by mammography is ~20%, either due to observer error or because the cancer is hidden by other dense tissue in the breast. While mammograms do save lives, improved mammography could lead to earlier and more accurate detection of breast cancer.

Which is why we were excited to see FDA clear CureMetrix to sell its software “triage” service to screen mammograms for signs of cancer. CureMetrix is based here in San Diego, and in March 2019, the company was given the green light to market cmTriage™, which according to the company’s website is “software intended to provide a notification triage code to the radiologist’s mammography work list based on the presence of a suspicious region of interest found by the underlying algorithm. This workflow optimization tool enables a radiologist to customize their mammography work list based on cases that may need immediate attention.”

According to CureMetrix CEO Kevin Harris, “the cloud-based service sends back the results in three to four minutes. What we’re seeing in preliminary studies is the triage software can help doctors read through their work list up to 40 percent faster.” In addition to having an impact on clinical efficiency, CureMetrix says radiologists can elect to get immediate notification of suspicious results, so patients can be made aware of a concern before they have even left the clinic.

We are definitely seeing more companies like CureMetrix, focused on leveraging artificial intelligence and deep learning to develop the next generation of medical image analysis technology, and FDA is working hard to keep pace. FDA recently published a Discussion Paper and Request for Feedback on the topic of Artificial Intelligence and Machine Learning in Software as a Medical Device. FDA is considering a total product lifecycle-based regulatory framework for these technologies that would allow for modifications to be made from real-world learning and adaptation, while still ensuring that the safety and effectiveness of the software as a medical device is maintained.

Artificial intelligence and machine learning technologies have the potential to transform health care by deriving new and important insights from the vast amount of data generated during the delivery of health care every day. Information is power…we just have to figure out how to harness it to better assist health care providers and improve patient care!

Further Reading:

  1. CureMatrix Website

  2. CureMatrix cmTriage™ Letter

  3. More Information on Breast Cancer – American Cancer Society

  4. What is a Mammogram – CDC

  5. Artificial Intelligence and Machine Learning in Software as a Medical Device



Med Device Monday – De Novo Clearance of The Miris Human Milk Analyzer

Breast milk is often considered a “superfood” for babies; it contains the appropriate vitamins, minerals, and nutrients to support a baby’s growth and development (not to mention hormones and enzymes that promote maturation and digestion, and antibodies that help the baby resist infection!). It’s no wonder why breast milk is often referred to as “nature’s first health plan.”

Yet for infants born preterm (before 37 weeks gestation), or with certain health conditions, breast milk may not contain sufficient protein or provide enough energy. For these infants with increased nutritional needs, knowing the macronutrient content of the breast milk being provided could give vital information to the health care team and parents, allowing them to make informed decisions on how to fortify the breast milk based on the individual needs of the infant.

In December 2018, the U.S. Food and Drug Administration permitted marketing of the Miris Human Milk Analyzer (HMA) to Miris AB of Sweden. The Miris HMA uses an infrared spectroscopy system to analyze samples of human milk, and provides a quantitative measurement of fat, protein and total carbohydrate content, as well as calculations of the total solids and energy content contained in the milk. The prescription device is intended for use by trained health care personnel at clinical laboratories, providing healthcare professionals with a new tool to aid in the nutritional management of newborns and young infants at risk for growth failure due to prematurity or other medical conditions.

FDA reviewed the Miris HMA test through the De Novo premarket review pathway, a regulatory pathway for low-to-moderate-risk devices of a new type. Along with its granting, FDA established a list of special controls to provide for the accuracy and reliability of tests intended to measure the nutritional content of human milk to aid in the nutritional management of certain infants. These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type. As discussed in our previous blogs about the De Novo pathway, this action also creates a new regulatory classification; meaning subsequent devices of the same type and intended use may go through FDA’s 510(k) process.

Already on sale in over 25 countries worldwide, the Miris HMA is now available to analyze breast milk and guide the individual nutrition of preterm babies in the U.S. The new device supports Miris’ mission, “to make individual nutrition, based on human milk, available globally to improve neonatal health.” We’re excited to see a new device on the market that has the potential to help one of the most vulnerable patient populations. Go babies!


Additional Reading:

1.      FDA Press Release

2.      De Novo Letter for The Miris Human Milk Analyzer

3.      NIH: Do breastfed infants need other nutrition?

4.      CDC: Breastfeeding

5.      Miris Website

MDMonday: NERV Technology's Implantable Biosensors

How is it October already? Soon it’ll be November and time to VOTE (don’t forget!)

Every year since we started the AcKnowledge RS blog, we’ve dedicated a month to medical devices that have not yet received FDA approval. It’s an easy way to see what cool things people are inventing, and maybe give you a small glimpse into the future. Who knows, you might be able to “ask your doctor whether Device XYZ is right for you” in the next few years!

This week we’re focusing on an implantable biochip by a company called NERv Technology Inc. This bioresorbable chip aims to help detect postsurgical complications by identifying internal bleeding, leakage of bodily fluids, and infection within the abdominal cavity. As described at the ne-rv.com website:

“NERv’s biosensors are predictive. They collect data and identify a specific kind of complication as soon as it develops. The biosensors provide information before the complication reaches a critical stage. NERv’s biosensors provide a preventative approach to post-operative care by identifying a complication as it is developing and preventing the development of further complications.”

A medical device that might be able to predict the future in order to prevent critical post-operative complications!? Someone call Tom Cruise and let him know Minority Report needs a remake!

Postsurgical Complications

Over 7,000 individuals die every year due to the failure or late detection of post-operative complications. Postsurgical or post-operative complications can result from the operation itself or other unrelated factors. Post-operative complications cause longer hospital stays and increased healthcare costs, not to mention the suffering that many patients (and their families) may go through. While it depends on the surgery, some common complications include pneumonia, internal bleeding, deep vein thrombosis, infection, and pulmonary embolism. The clinical signs of disease are often blurred in the postoperative period. Early detection of postoperative complications requires repeated evaluation of the patient by the operating surgeon and other team members, which can be time consuming and laborious for everyone involved. Additionally, some of these complications take days or weeks to show up, often well after you’ve gone home to recover. The current methods for detecting post-operative complications include imaging techniques like CT and MRI scans, as well as lab tests which are only performed once the patient has demonstrated certain symptoms…and these all of course take you out of your comfy recovery chair at home and bring you back to the hospital. Which is good if you do need to go to the hospital, and not-so-good if it turns out to be an unnecessary visit.

Screenshot from www.ne-rv.com/

Screenshot from www.ne-rv.com/

How does the device work?

The NERv biochip is about the size of a shirt button, and is implanted into the body during surgery. As soon as a complication develops post-surgically, the chip is able to detect it and collect information about its status. The data are sent to a receiver located in a trans-dermal patch placed on the wound after surgery. While the patient may receive a simple alert notification so that they are able to seek medical care right away, the physician will get a more detailed analysis of the patient’s status. The biosensors in the chip have demonstrated to be very sensitive; able to detect even small changes of specific biomarkers associated with these complications. Physicians will also be able to get information on the kind, location, and severity of the complication. Made of bioresorbable materials, the biochip sticks around for a month before it is broken down by the patient’s body, thus avoiding another surgery to have it removed.

We’re excited to see medical devices like this being developed! We look forward to keeping tabs on NERv…and watching this technology get to market and safely into patients!

Additional Information:

1. NervTech Website

2. NERv Illustration Animation