FDA

FDA Friday - Song P. Seto, PhD

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 info@acknowledge-rs.com.


I didn’t have much knowledge about medical device regulation before joining FDA, so I had a lot to learn in the beginning. However, I was very open to learning new things and willing to ask questions. In return, I offered my knowledge and experience to help other reviewers.
— Song P. Seto, PhD
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Dr. Seto received her doctorate degree in Bioengineering from the Georgia Institute of Technology, following a Master of Science degree in Education from Pace University and a Bachelor of Science degree in Bioengineering from the University of California, Berkeley. Song’s academic research background in biomechanics and regenerative medicine prepared her well to review complex and varied pre-market submissions, including 510(k), 513(g), De Novo, and Pre-Submission (including pre-IDE) applications. In her role at FDA, Song reviewed the safety and effectiveness of medical devices such as bone void fillers, bone cements, and soft tissue replacement devices for the Restorative and Repair Devices Branch.


Tell us a little bit about your time at FDA.

I joined FDA, specifically the Center for Devices and Radiological Health (CDRH), in 2014, straight out of graduate school. I was a Lead Reviewer for pre-market submissions in the Restorative and Repair Devices Branch of the Division of Orthopedic Devices, which was a good fit given my research background and interests. I reviewed pre-market submissions independently, as well as managed review teams of subject matter experts. One of the nice things about working at the FDA was the opportunity to participate in various activities and training. I participated in Quality Systems training, worked on authoring guidance documents, helped with biocompatibility training, worked on standards, and had the opportunity to plan a FDA-wide Bone Imaging Workshop for over 180 participants.

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

There are a many things I really enjoyed. The level and manner of collaboration were great. For example, I worked with subject matter experts that worked really hard to get me the information I needed within some tough deadlines. While working on a submission, everyone was congenial and had the same goal to review a submission with scientific rigor within the regulatory framework.

I also really enjoyed having a variety of experts on the review teams. Subject matter experts often have had past careers, significant research experience, or a long career at FDA that provides important context when reviewing a submission. There were numerous times I pulled a medical doctor or former veterinarian aside to ask about a certain procedure, and I learned so much from their experience in their respective fields. The wealth of experience and knowledge at FDA was truly remarkable and accessible.

You mentioned you worked as a reviewer within the Restorative and Repair Devices Branch. Can you describe the range of devices your group reviewed?

The Restorative and Repair Devices Branch (RRDB) reviews submissions on orthopedic bone void fillers, polymethyl methacrylate (PMMA) cements, scaffolds with bone morphogenetic proteins, intraarticular hyaluronic acid, and many types of soft tissue replacement devices (many in the concept stage). RRDB also sees quite a few combination products for devices that also have biologic and/or drug actions.

What past experience or trait do you think helped you be a successful reviewer?

I didn’t have much knowledge about medical device regulation before joining FDA, so I had a lot to learn in the beginning. However, I was very open to learning new things and willing to ask questions. In return, I offered my knowledge and experience to help other reviewers. It was beneficial to be detail-oriented and organized, as there was a lot of information to digest. Good writing skills were also crucial, because much of the work as a reviewer is preserved through writing, which will help future reviewers understand the decision process. Although my past research experience did not directly impact my work on a regular basis, it did prepare me to quickly analyze data and understand the scientific principles that the medical device technology was based on.

What are you up to these days?

I am currently a Technical Writer for the Florida Space Institute. I know, very different from my regulatory background! Lately, I’ve been reading and writing about in situ resource utilization and how to get humans deeper into space. I also have a side gig as a Scientific Consultant for a firm who performs research as a federal contractor and prepares many Small Business Innovation Research (SBIR) proposals. When I left FDA, I was looking for a more flexible work option, and the opportunity arose to use my skills in a different field. I enjoy writing and supporting researchers, so personally it was not a huge leap. And like my position at the FDA, my current position requires me to be open to learn and to be an effective communicator. I am not totally over with medical device regulation, however. I’ll be looking into getting back into it soon.

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

How to manage multiple deadlines. Also, to ask questions that seem pertinent to either understanding the proposal or the premise of the proposal that the principal investigator wants to get across.

How is working in industry similar and/or different than working at FDA?

In my current industry, I interface primarily with research scientists and faculty. Let’s just say that most meetings with scientists and faculty (in Florida, to boot) are much more casual than sponsor meetings at FDA. However, preparing research proposals is similar to preparing regulatory submissions in the sense that many times they are sent to a government agency for review. There is still the need to communicate concisely and effectively.

What is some advice you can give to a person interested in regulatory affairs?

I would suggest speaking to a variety of experts in the field; there are many more aspects of regulatory affairs than just getting a product to market.

For anyone interested in working at FDA, I suggest getting in touch with someone in your network that works there. I learned a lot about the culture and responsibilities of being a pre-market reviewer from a former lab mate, and he was instrumental in helping me join FDA.

For those interested in the FDA, I also like suggesting that they read a history of the agency. There are several well-written books out there that highlight the agency’s role in protecting the public’s health. As a reviewer, gaining a better understanding of the FDA’s mission to protect public health and safety allowed me to keep the greater goals of the agency in mind while working closely with industry to bring innovative products to market.


More about Song P. Seto, PhD

For more information about Song, please visit her LinkedIn page. For information about Song and her colleagues’ work at FSI, please click here. To learn more about the Small Business Innovation Research (SBIR) program, please click here.

MDMonday: MiniMed 670G Glucose Monitor and Insulin Pump for Pediatric Populations

 Image from http://www.medtronicdiabetes.com/

Image from http://www.medtronicdiabetes.com/

 

In September of 2017, FDA approved a device for patients with type 1 diabetes aged 14 and up. The device, called the MiniMed 670G, is a hybrid, closed-loop system that provides automated insulin delivery with little to no input from the user. The system includes a glucose-measuring sensor that attaches to the body, an insulin pump that straps to the body, and an infusion patch that connects to the pump with a catheter. This catheter is the way through which the insulin is delivered. Very recently, FDA expanded the approval of this device for use in younger pediatric patients, which now include children aged 7 to 13 with type 1 diabetes.

In patients with diabetes, the body’s ability to make or react to insulin is impaired, and doesn’t function correctly. The pancreas makes little or no insulin in people who have type 1 diabetes. This means that they must keep track of their glucose levels throughout the day, and inject insulin at certain points so they can avoid high glucose levels. FDA Commissioner Scott Gottlieb, M.D. recognizes the struggle for patients with type 1 diabetes, and stated, “Caregivers and families of young patients with diabetes face unique challenges in managing this disease, in particular the round-the-clock glucose monitoring that can be disruptive to people’s lives.” The MiniMed 670G helps to combat hypoglycemic episodes by measuring the glucose levels of the user every five minutes, and automatically adjusting insulin levels by either withholding insulin or administering it. While the device can adjust insulin levels automatically, users must manually request insulin to counter the consumption of carbohydrates at any mealtime.

For this approval, FDA analyzed data from clinical trials of the MiniMed 670G that spanned 105 individuals, aged 7 to 11 years of age. Each participant wore the device for just over three months, and participated in three different phases of the study so both at-home use and remote use could be monitored. At the conclusion of the study, no serious adverse events were found associated with the MiniMed 670G, and it was determined that the device was safe for use in those aged 7 to 13 with type 1 diabetes. FDA Commissioner Scott Gottlieb, M.D. states that, “Advances in science, technology and manufacturing are contributing to the development of new and expanded uses of products that can help improve the quality of life for those with chronic diseases, especially vulnerable populations, like children. Today we’re extending these opportunities to younger children who are especially vulnerable to the impact of this disease, such as the disruptions in sleep that can be caused by the need for frequent blood glucose checks. The FDA is dedicated to promoting policies that support the development of new technologies based on these advances, and to ensuring that the path to market is both efficient and effective.”

Getting treatments to pediatric populations has been an ongoing goal for both FDA and industry. Historically, medical device manufacturers and investors have been wary of expanding their products to children as the risk was seen to be too great. Nobody wants to see injured kids due to a medical technology...it's bad for business and clearly bad for the children, their families, and their healthcare providers. With this in mind, FDA has implemented policies in the past few years (e.g. sections of the 21st Century Cures Act) that helps industry help children. Getting much needed technology scaled to be appropriate for children is critical to help these populations get the treatment they need! We applaud medical device manufacturers who are (safely) working on treating these vulnerable populations.

Further Reading:

  1. FDA and Pediatrics

  2. 21st Century Cures Act: Sections that Impact FDA

  3. Press Announcement about MiniMed670G Approval

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/