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

FDA Friday - Dulciana Chan, M.S.E.

This #FDAFriday series consists of mini-interviews with former FDA regulators. Our goals are twofold: (1) help students and professionals interested in Regulatory Affairs see what career paths are possible, and (2) talk about some of the various roles at FDA to demonstrate the diversity of responsibilities at the Agency. If you are a former FDA employee and would like to participate, please email us at

A common mistake that manufacturers make in their Investigational Device Exemption (IDE) submissions is not having a plan to deal with missing data. It is important to have a plan upfront so that the data from all patients can be used.
— Dulciana Chan, M.S.E.
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Dulciana Chan received her B.S. in Biomedical Engineering from Johns Hopkins University in 2002, and her M.S.E. in Bioengineering from the University of Maryland in 2010. Directly following her undergraduate degree, Dulciana began her FDA career as a research associate in the Center for Devices and Radiological Health (CDRH), Office of Science and Engineering Laboratories (OSEL). A year later, she became a Biomedical Engineer at FDA, and for 14 years operated in various branches of the administration, including as a scientific reviewer and policy analyst in the Office of Device Evaluation (ODE), and as an OSEL principal investigator.

While working at FDA, Dulciana received numerous honors and awards, including the 2014 CDRH Honor Award and the 2014 FDA Scientific Achievement Award for Excellence in Analytical Science. Dulciana has extensive experience in the areas of electromagnetic compatibility (EMC) testing and electrical safety, and is an asset to Acknowledge Regulatory Strategies, where she is a Senior Regulatory Specialist.

Tell us a little bit about your time at FDA.

I started at the FDA as a research associate in the Center for Devices and Radiological Health (CDRH) in the Office of Science and Engineering Laboratories (OSEL). I worked on several research projects and gained skills including computational modeling and electromagnetic compatibility. One of my main projects focused on optical recording of cardiac myocyte monolayers to study cardiac arrhythmias. After my first year at FDA, I also became a scientific lead reviewer in the Office of Device Evaluation (ODE). Fortunately, I was able to continue performing research in OSEL while doing premarket reviews for devices in ODE for the next 14 years.

Can you tell us a little more about your research in the Office of Science and Engineering Laboratories (OSEL)?

The lab I was in began to use pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias. It was part of a larger program to predict drug proarrhythmic risk in cells prior to the clinical studies that are required for new drugs. This research was very rewarding in clinical relevance and scope.

You also worked as IDE staff while you were at FDA. What was one of the common mistakes you saw companies make when submitting their clinical study to FDA?

A common mistake that manufacturers make in their Investigational Device Exemption (IDE) submissions is not having a plan to deal with missing data. It is important to have a plan upfront so that the data from all patients can be used. The reality is that there will be missing data, whether from a patient missing a follow-up or a missing test or outcome. However, with preplanning, the data can still be interpreted correctly.

What was your favorite thing about working with a review team on a premarket notification/approval submission?

One of the benefits of working with a review team is being able to access the knowledge of an expert. Often there may be an aspect about a device that you only have high level knowledge about. The review team can quickly explain the technicalities to you in a meaningful way. Their expertise might also help in identifying potential problems.

What past experience or trait do you think helped you be a successful reviewer/during your tenure at FDA?

I think being a lifelong learner helped me be a successful reviewer. Some might see the process of reviewing medical devices as repetitive. However, I found that each product provided a unique learning experience due to the many types of devices, regulation pathways, and emerging public health issues to learn about. There were endless ways to learn new things at the FDA.

What were your favorite FDA submissions to work on and why?

My favorite FDA submissions were IDEs because I learned about the details of a clinical study and about an emerging technology or trend. It was also nice to ensure that all the aspects necessary for a successful clinical study were planned out. Although there was pre-clinical work performed before an IDE submission, it was interesting to see a device at the beginning of its regulatory path.

What's something that you learned from FDA that helped you in your current position?

Working at FDA helped me learn team communication and managing expectations. Everyone’s time is valuable and it is important to make the most of team meetings. When leading a team, I aim to let each member of the team know the goal, their responsibility, and potential outcomes.

How does your current role incorporate or benefit from your regulatory experience?

Many times, companies are not sure what to submit to the FDA so they submit everything (test report and data), which can be overwhelming to an FDA reviewer. I think my regulatory experience can help companies determine what to submit so that they clearly show they meet all FDA requirements.

More about Dulciana Chan, M.S.E.

For more information about Dulciana, please visit her LinkedIn page.

Med Device Monday: ClearMate - Effective Carbon Monoxide Poisoning Treatment granted via De Novo Pathway

Have you heard the saying, “canary in a coal mine”? Well, the saying started because canaries were actually used in coal mines (until 1986!?) to detect dangerous levels of the gas carbon monoxide. With a faster metabolism, canaries show the effects of poisoning by the colorless, odorless gas before the carbon monoxide levels become critical for workers. While many homes and businesses now have electronic carbon monoxide detectors (canaries everywhere rejoice!), inadvertent carbon monoxide exposure and poisoning is still a major issue worldwide.

According to the Centers for Disease Control and Prevention, carbon monoxide poisoning is the most common type of poisoning in many countries, and is responsible for over 20,000 emergency room visits per year in the US. Carbon monoxide gas is produced primarily by motor vehicles and poorly maintained and/or poorly ventilated heating systems, gas stoves, or gas-powered generators. It is particularly dangerous due to its ability to outcompete oxygen for its spot on hemoglobin, the protein in red blood cells that typically carries oxygen from the lungs to the rest of the body. The affinity between hemoglobin and carbon monoxide is approximately 230 times stronger than that between hemoglobin and oxygen.

As a result of exposure to carbon monoxide, an individual may suffer symptoms including headache, dizziness, weakness, upset stomach, vomiting, chest pain and confusion. Exposure to high levels of carbon monoxide can cause death in minutes. The standard treatment for carbon monoxide poisoning is to have the patient breathe 100 percent oxygen through a mask. In severe cases, a hyperbaric chamber may be used, which delivers oxygen under higher than normal pressure. However, according to Dr. Malvina Eydelman, director of the Division of Ophthalmic, and Ear, Nose and Throat Devices in the FDA's Center for Devices and Radiological Health, “hyperbaric treatment, which is necessary for severe carbon monoxide poisoning, is less accessible because there are only 60 medical centers with hyperbaric units in the entire US. Moreover, those medical facilities are seldom in rural areas, so treatment in those areas could be delayed considerably due to transport time.”

On March 14th, 2019, the FDA granted marketing authorization of ClearMate to Thornhill Research, Inc. ClearMate, which is intended to be used in an emergency room setting to help treat patients suffering from carbon monoxide poisoning, is designed to quickly remove carbon monoxide from the body by increasing a patient’s respiration rate. The device consists of a gas mixer, valves, meters, breathing circuits, an oxygen reservoir, a mask, and hoses. By delivering both 100 percent oxygen to the patient, as well as a mixture of oxygen and carbon dioxide, the patient breathes faster. More rapid breathing accelerates the rate at which the carbon monoxide leaves the patient’s body, allowing a normal amount of oxygen to attach to hemoglobin and be carried to where it is needed throughout the body. In clinical studies, using ClearMate resulted in faster elimination of carbon monoxide than treatment with 100 percent oxygen alone (although not faster than hyperbaric oxygen therapy).

Per the Thornhill Medical website:

“The compact, 6 Kg, ClearMate™ is totally pneumatic – no electricity, batteries or computers are needed for it to work. ClearMate™ was designed for rescue vehicles, hospital emergency departments, factories, schools, and any other facilities where the earliest possible treatment of CO [carbon monoxide] poisoning will save lives. Whenever carbon monoxide poisoning may have occurred, ClearMate™ can be used on the scene by anyone with minimal training, and with no risk of side effects.”

ClearMate was reviewed under the FDA’s De Novo premarket pathway, the regulatory pathway for low-to-moderate-risk devices of a new type. Approval through the De Novo pathway establishes 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 notification process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.

So while canaries can let out a sigh of relief, so can patients who might need this device. Previous to the De Novo, ClearMate achieved CE Marking, and was also approved for sale in Canada, Australia, China, Korea and Taiwan. Now that this device is available in the US, Americans who might experience carbon monoxide poisoning have a better chance of survival…and that’s all something we can breathe easier about!

Additional Reading:

  1. FDA Classification Order for ClearMate

  2. FDA Press Release for ClearMate

  3. More information on the ClearMate Device

  4. More information about carbon monoxide poisoning

Med Device Monday: INNOVO – Therapy Device to Treat Stress Urinary Incontinence granted via the De Novo Pathway

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Urinary incontinence is a very common, often ignored health issue. Stress incontinence is the most common type of urinary incontinence, and describes accidental leaks that occur when coughing, sneezing, laughing, jumping or doing heavy lifting. These simple movements, or stressors, put pressure on the bladder. Unfortunately, when the pelvic floor muscles are weak, this pressure can lead to a messy and potentially embarrassing leak. In women, stress urinary incontinence (SUI) can happen at any age, however it is most common during pregnancy, after childbirth, and during stages of menopause.

In November of last year, FDA granted a De Novo automatic reclassification to Atlantic Therapeutics’ INNOVO therapy device to treat stress urinary incontinence in women. INNOVO is a wearable device that may be prescribed as a front-line therapy to those suffering stress urinary incontinence, or as a second line therapy to those that previously failed physical therapy (in the form of supervised or unsupervised pelvic floor exercises, also known as Kegel exercises).

So, what exactly is a pelvic floor?

The term pelvic floor describes the group of muscles that span the bottom of the pelvis and support the pelvic organs. The pelvic organs in men (yes, men also have a pelvic floor) are the bladder and bowel, and in women they are the bladder, bowel and uterus. Weak pelvic floor muscles can lead to incontinence, pain, and prolapse, or the slipping down or forward of a pelvic organ. Honestly, we can’t think of anything good that comes from a weak pelvic floor.

According to the manufacturers, using a hand-held controller that is attached to a two-part garment, the INNOVO therapy device sends targeted impulses via conductive pads (attached to your upper thigh and buttocks) to activate the muscles of the pelvic floor. It is a technology that has been designed to optimally strengthen your pelvic floor with 180 contractions per session, allowing the device to do your pelvic floor exercises for you.

The device has demonstrated promising results. 87.2% of patients were dry or almost dry of after a 12-week treatment period, with 93% of patients experiencing improvement in as little as four weeks using the device five days a week for 30 minutes. One potential benefit of the device is that it is a transcutaneous electrical stimulator that offers a non-invasive choice to treat stress urinary incontinence. Elizabeth LaGro, Vice President of The Simon Foundation for Continence said it well, “INNOVO offers a new frontline therapeutic option for the millions of American women living with stress urinary incontinence, and in a significant group could delay or prevent the need for higher risk surgery or medical intervention.”

And finally, in addition to talking about a novel device coming soon to the US market, this week’s Medical Device Monday gives us the opportunity to again mention the De Novo pathway. In December, now outgoing FDA Commissioner Dr. Scott Gottlieb provided a high level description of the pathway; “the De Novo pathway for novel medical devices allows the FDA to conduct a rigorous review of new technologies so that patients have timely access to safe and effective medical devices to improve their health”. In practice, the De Novo pathway is used for the review of novel, low to moderate risk devices for which there are ways to provide reasonable assurance of the device’s safety and effectiveness, but for which there is no existing predicate to use in the determination of substantial equivalence. So now, after years on the European market, women in the US will soon have access to INNOVO. We hope to see more US moms on trampolines in the near future!

Additional Reading:

1.      FDA Classification order

2.      Atlantic Therapeutics website

3.      Video explaining how INNOVO works

4.      Press release

5.      More info on SUI

Med Device Monday: Recall of the Raindrop Vision Inlay Device

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In April 2017, we wrote about a new device called the Raindrop Vision Inlay, manufactured at the time by ReVision Optics. Approved in 2016, the device is basically a small implantable contact lens that reshapes the front of the eye and corrects presbyopia, more commonly known as farsightedness. A little over two years later, the Raindrop Vision Inlay was the subject of an FDA Safety Communication recommending patients not receive the device. After post-market research, FDA identified an increased risk of corneal haze, or the development of a cloudy layer within the eye that impairs overall vision. Shortly thereafter, in November 2018, FDA issued a Class I recall - the most serious type of recall - reserved for devices that may cause serious injuries.

So, what happened?

Going back to 2016, the Raindrop Vision Inlay was given FDA approval in large part due to a two-year clinical trial that yielded promising results, including high numbers of patients who could read smaller print at closer distance post-op. At the time of device approval, the clinical study showed that while 16.1% (60 of 373) of patients had central corneal haze of any severity at some point during follow-up, the percentage of patients with two or more lines of loss in vision on the eye chart caused by corneal haze was 1.1% (4 of 373 patients). The number of patients who had the device removed was 24 of 373 patients (6.4%) at the two-year follow-up visit, with 29% of those device removals (7 of 24 patients) being due to corneal haze.

The Raindrop Vision Inlay was marketed under the conditions that the device be restricted to prescription use and specifically labeled to define the training or experience practitioners needed in order to implant the device. Marketing of the device was also conditional on the reporting of results from two post-approval studies (PAS), one that followed patients enrolled in the original clinical study, and a second that tracked newly enrolled patients. Of the 373 patients from the original study, 150 were enrolled in the PAS. The most recent data from the ongoing study, including 5 years of follow-up in some patients, showed that the rate of central corneal haze, at any time during the study, was 42% (63 of 150 patients), and that the presence of haze at any location within the cornea was a whopping 75% (113 of 150 patients). The percentage of patients with two or more lines loss on the eye chart caused by corneal haze remained low at 2.0% (3 of 150 patients), however that was greater than what was observed during the original clinical study. After evaluation of the PAS data, the risks outweighed the benefits of the device and lead the company and FDA to initiate the recall.

It is awful that the Raindrop Vision Inlay caused any patients implanted with the device to suffer, and one might be quick to judge that FDA ‘screwed up’ by allowing an unsafe device to be sold. The whole story is quite a bit more complicated, however, and we feel the Raindrop Vision Inlay situation is an example of FDA working to uphold its mission. In this situation, FDA took responsibility for both helping speed innovation that would potentially improve patient’s lives, and for ensuring the safety and effectiveness of a medical device before and after market approval.

FDA closely monitors reports of adverse events and other problems with medical devices, and alerts health professionals and the public when needed to ensure their proper use. FDA has stated that it is currently working with the owner of the Raindrop Vision Inlay, Optics Medical, on a plan to collect any remaining devices already distributed. FDA will continue to gather and evaluate data related to the recalled device, and communicate new information as warranted.

Further Reading:

1. FDA Safety Communication

2. Raindrop Vision Inlay PMA Approval Letter

3. Summary of Safety and Effectiveness Data

4. Raindrop Vision Inlay Recall Notice