FDA

FDA Friday - A Closer Look at the CDRH Health of Women Program

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In early September, FDA released their strategic plan for the Health of Women Program, a program within the Center for Devices and Radiological Health (CDRH) that aims to explore the unique issues related to the performance of medical devices in women. The 41-page document outlines the agency’s mission, vision, and efforts to better understand and address the impact of sex- and gender-specific issues on medical technology design and development, clinical and non-clinical study design, and other medical device-related matters. This is a huge win for women who are patients…so this pretty much means ALL women (US and abroad) should hopefully benefit!

For years, both FDA and the scientific community have been aware that sex and gender can play a significant role in the course and outcome of conditions that affect all organ systems. The agency states that the Health of Women Program will address “health conditions that are specific to women, as well as conditions that are more common or more serious in women, have distinct causes or manifestations in women, have different outcomes or treatment options in women, or have higher morbidity or mortality in women”.

Evidence shows that sex and gender can impact numerous disorders, including cardiovascular disease, pulmonary dysfunction, neurological debility, irritable bowel syndrome, endocrine and autoimmune disorders, and mental illness. The program’s vision is to ensure that, “patients, caregivers, and providers have timely access to high quality, safe, and effective medical devices that perform optimally in women, as well as access to relevant and understandable sex- and gender-specific information about medical devices that can be used to make informed health care decisions”.

The CDRH Health of Women Program has initially prioritized three focus areas:

  1. Sex- and gender-specific analysis & reporting

  2. An integrated approach for current & emerging issues related to the health of women

  3. A research roadmap

With regard to sex- and gender-specific analysis and reporting, FDA intends to improve the availability, analysis, and communication of sex- and gender-specific information for the safe and effective use of medical devices. The goal is to improve and better understand the performance of medical devices in women. The Health of Women Program also aims to build and strengthen programs and initiatives across CDRH to improve the overall health and quality of life for women. The plan is to bring together CDRH offices, device manufacturers, scientists and patients in order to coordinate and develop an integrated approach to deal with current and emerging women’s health issues. Finally, FDA has made it clear that the program will support the development of a research roadmap to identify and address gaps and unmet needs, as well as promote regulatory science, as it relates to the health of women.

The strategic plan for the Health of Women Program aims to “bring together industry, clinicians, researchers, patients, academia, government agencies, advocacy groups, and all customers in an effort to encourage innovations in research study design, device development, and appropriate ways to share information with women and their health care providers to help them make informed decisions about which device may best meet their needs.”

In addition to introducing the CDRH Health of Women Program and detailing the framework by which the program will address the steadily growing importance of women’s health, the strategy document provides several additional, thoughtful sections detailing the scientific rational behind the program. In the appendix, the document discusses the history of male predominance in research, the fact that sex is a basic biological variable, and how gender is a clinical variable. The CDRH Health of Women Program Strategic Plan recognizes the importance of addressing sex- and gender-specific issues in medical technology design, development and implementation, and details the program’s plans to provide the highest quality of innovation, safety, and effectiveness to every patient.

The CDRH Health of Women Program welcomes comments and feedback on the outlined Strategic Plan, and encourages other ideas and suggestions on how they can strengthen the collection and dissemination of information associated with sex and gender related devices.

Comments and feedback can be sent to docket number FDA-2019-N-3804 in the Federal Register.

You can also send your questions about CDRH’s Health of Women Program to: CDRHHealthofWomen@fda.hhs.gov

FDA Friday - Understanding STeP - FDA's Proposed Safer Technologies Program

This month has been chock-full of new guidance documents released by FDA; draft guidances, updated documents, strategic plans, and more! A draft guidance that was released last Thursday, September 19th, caught our attention here at AcKnowledge RS, and we want to share with you what it’s all about.

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The document released last week, “Safer Technologies Program for Medical Devices,” provides an in-depth look at a new program that will hopefully be implemented in the near future at FDA. The Safer Technologies Program, or STeP, has been designed to complement the Breakthrough Devices Program. According to the new draft guidance document, STeP is a voluntary program that will be introduced for medical devices and combination products that are expected to, “improve the safety of currently available treatments or diagnostics that target an underlying disease or condition associated with morbidities and moralities less serious than those eligible for the Breakthrough Devices program” (lines 104-107). FDA believes that the program will provide a public health benefit because the program aims to expedite the review process for medical devices that offer a significant safety advantage in treating or diagnosing diseases or conditions that are serious, but not so serious or debilitating as to make the device eligible for the Breakthrough Devices Program.

Inclusion in STeP requires a sponsor to submit a written request for inclusion via a Q-submission, and for FDA to then agree the device is a good fit for the program. The guidance document explains that as part of the Q-submission, sponsors will demonstrate their device’s eligibility by meeting and addressing the general and specific eligibility factors. To meet the general eligibility factor, the device should be subject to review under a premarket approval application (PMA), De Novo classification request, or premarket notification (510(k)). To meet the specific eligibility requirement, the device must not be eligible for the Breakthrough Devices Program, and significantly improve the benefit-risk profile of the device through substantial safety innovation. The safety innovation must provide one or more of the following:

(1) a reduction in the occurrence of a serious adverse event that is known,
(2) a reduction in the occurrence of a known device failure mode,
(3) a reduction in the occurrence of a known use-related hazard, or
(4) an improvement in the safety of another device or intervention.

Although the program is not yet active and no submissions are currently being accepted, comments on the draft guidance are welcomed until the close of the comment period (submit comments here until 11/18/2019). Only after FDA issues the final guidance will submissions be accepted for review. STeP has the potential to offer sponsors the opportunity to engage in a more expedited review process, even if their device does not qualify for the Breakthrough Devices Program, and the prospect of an opportunity to quickly bring substantial safety innovations to market is something we’re really excited about!

Further reading:

FDA’s Safer Technologies Program - STeP Guidance Document & Press Release

FDA’s Breakthrough Devices Program - Description

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

FDA Friday - Robert Allen, 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 really enjoyed working with FDA reviewers and managers. You might think that FDA employees are focused on just rules and red tape, however, people there are very passionate about public health, and creative in getting things done that benefit patients within the framework of rules and regulations.
— Robert Allen, PhD
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Dr. Allen received his bachelor’s and doctorate degrees in Bioengineering from the University of Pittsburgh, Swanson School of Engineering. As a Ph.D. candidate, his research focus was in cellular and medical product engineering. In 2015, he began work at FDA as an American Institute for Medical and Biological Engineering (AIMBE) Scholar. After completing his tenure as an AIMBE fellow, Dr. Allen joined the FDA’s Center for Devices and Radiological Health (CDRH) as a biomedical engineer and staff fellow. Robert acted as a lead reviewer in the former Division of Cardiovascular Devices, coordinating the review of premarket regulatory submissions such as 510(k)s, Pre-Submissions, and various supplements for Investigational Device Exemption (IDE) and Pre-Market Application (PMA) submissions. He also worked as a biocompatibility consulting reviewer, evaluating the potential biological response patients could have to a medical device.


Start off by giving us some more detail about your time at FDA.

I spent three years at FDA. For the first nine months, I was an American Institute for Medical and Biological Engineering (AIMBE) Scholar, working on strategic projects for the Center for Devices and Radiological Health (CDRH). Afterward, I became a premarket device reviewer for CDRH. My titles included “Biomedical Engineer” and “Staff Fellow”, and my roles included Lead Reviewer and Biocompatibility Consulting Reviewer for the Division of Cardiovascular Devices (now referred to as DHT2B), Vascular Surgery Devices Branch (now known as the Vascular and Endovascular Devices Team).

Tell us a little more about being an American Institute for Medical and Biological Engineering (AIMBE) Scholar. Can you briefly describe the program and talk about your responsibilities in that role?

The AIMBE Scholars program is an opportunity for early career PhDs in biomedical engineering or related fields to serve as expert advisors to policy makers at CDRH. The first cohort of AIMBE Scholars started at FDA in 2014. To date, AIMBE Scholars have worked on a wide range of projects aimed at improving the review process, providing tools to support regulatory decision-making, and developing policies to promote innovation and public safety. More information on the program can be found at https://aimbe.org/scholars-program/.

My AIMBE Scholar appointment was with the Office of Device Evaluation (now known as the Office of Product Evaluation and Quality, or OPEQ), where I assisted with efforts to reclassify a large number of medical devices. Reclassification is a process that impacts the regulatory requirements for each reclassified device. It is a complex process involving multiple teams across CDRH. To coordinate this process, I needed to learn the details of the process, then guide each team through it. This involved project management and lots of internal written and verbal communication. Throughout the process I worked with upper management, middle management, and individual premarket reviewers.

In addition to our FDA projects, AIMBE Scholars also attended site visits to current and potential industry sponsors. We also presented our projects at the AIMBE Annual Meeting to academic and industry members of AIMBE. These were great opportunities to network and hone our regulatory communication skills.

What about your experience as an AIMBE scholar made it clear to you that you wanted to spend more time at FDA?

Two things: the public health impact of FDA’s work, and the people at FDA. Regarding public health impact, it was fulfilling to work on projects where the immediate goal was to benefit public health. Prior to this work, I was a graduate student developing early-stage technologies that might one day help patients. While such research could be important in the long-term, it takes many years to prove a new technology, and many more years to develop a medical product and obtain regulatory approval/clearance. In contrast, the work I did at FDA changed the regulatory requirements for each reclassified device, which directly impacts the speed and cost to develop and market new products in that device category. It was thrilling to be able to see how my work could have a positive impact on patients in the short term.

Regarding people, I really enjoyed working with FDA reviewers and managers. You might think that FDA employees are focused on just rules and red tape, however, people there are very passionate about public health, and creative in getting things done that benefit patients within the framework of rules and regulations.

You worked as a lead reviewer in the Vascular Surgery Devices Branch. Before your time at FDA, what was your experience with blood-contacting cardiovascular devices?

Prior to FDA, I helped develop a resorbable vascular graft, which is a blood-contacting permanent implant. This was part of my dissertation work as a graduate student at the University of Pittsburgh, under the mentorship of Dr. Yadong Wang. That work helped me to understand how device materials interact with blood. I also learned about the design requirements for implants that need to withstand and maintain blood pressure, and the various failure modes to watch for.

While this experience was certainly helpful to my work as a lead reviewer, it was not a prerequisite for the job. After starting as a reviewer, I learned that FDA considers a wide range of backgrounds for lead reviewers, though they are most commonly engineers or scientists. Additionally, most of what I needed to know I learned on the job. FDA review teams have a wealth of collective experience and scientific knowledge about their devices. Coming in as a fresh Ph.D., I certainly did not know even 10% of what it takes to review a device. But the review team did and they got me up to speed quickly.

What was your favorite thing about working with a review team on a premarket notification (510(k)) or premarket approval (PMA) submission?

I enjoyed “standing on the shoulders of giants”, so to speak. I had the privilege of working with seasoned scientists, engineers, medical officers, and veterinary officers. I learned so much from these FDA veterans over the course of my premarket reviews. Much of their insight comes uniquely from experience reviewing devices, so it felt like I was learning things I couldn’t learn anywhere else.

What does it mean to be a biocompatibility reviewer?

Here is my personal take on what a biocompatibility reviewer does: Biocompatibility reviewers focus on reviewing the potential biological response that a patient can have to a medical device. Practically speaking, this means that biocompatibility reviewers review a combination of in vitro and in vivo testing, risk assessments, and rationales for why testing is not needed. These tests, risk assessments, and rationales focus on the impact of the device, or chemicals that can leach out of the device; on the patient’s cells/tissues, blood, and organ systems.

Biocompatibility review is just one of many roles that a premarket device reviewer can play at FDA. For example, I served as both a lead reviewer and a biocompatibility reviewer for premarket device submissions.

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

When I started review work, I thought that my technical expertise would be my most valuable asset for day-to-day work. While it certainly came in handy, the skills that helped me most were actually my communication and consensus building skills. Review teams often include multiple experts with a range of technical backgrounds and communication styles. To complete a review efficiently, we all needed to find common ground regarding priorities, action items, and ultimately, the safety and effectiveness of the device.

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

I enjoyed reviewing 30-Day Notices for manufacturing changes. In reviewing these submissions I got to see some of the manufacturing steps for the device, then evaluate and/or question the thought process behind each manufacturing change. This was fun because I got to see how devices are made; there are a wide range of manufacturing techniques out there, and some of them are fascinating. For the techniques that I already knew well from graduate school, it felt satisfying to leverage my existing knowledge to expedite a review.

What are you up to now and how does your current role incorporate your regulatory experience?

I currently work as a Senior Associate within the Regulatory Affairs team at MCRA. MCRA is a leading advisory firm and Contract Research Organization (CRO) for the medical device industry, with a range of services including regulatory, reimbursement, clinical research, healthcare compliance, and quality assurance. As a Regulatory Affairs Senior Associate at MCRA, I help our US and international clients to write and submit regulatory submissions to achieve and maintain market approval/clearance. These submissions include US FDA submissions, such as 510(k)s, Investigation Device Exemptions (IDE), and Premarket Approvals (PMA). They also include international submissions such as Clinical Evaluation Reports (CER). We also help our clients to develop and execute long-term regulatory strategies.

My FDA experience translates well to my work as a regulatory consultant. I am constantly using my firsthand knowledge of FDA’s regulatory expectations when I write premarket submissions for MCRA’s industry clients. The translation is direct for cardiovascular devices and biocompatibility evaluations, since I worked on those two specific things at FDA. For other device types and different types of testing, I can extrapolate from what I know, while also leveraging the experience of other MCRA employees. One of the great things about working at MCRA is the depth of experience that MCRA has in a range of product areas. For example, if I’m working on an orthopedic device submission, I can ask any of our 5 former FDA orthopedic device reviewers for their firsthand knowledge. I can also borrow the experience of MCRA’s other seasoned regulatory consultants who have a long track record of developing successful orthopedic device submissions.

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

As a regulatory consultant, I’m writing rather than reviewing device submissions. However, the process of writing submissions is very similar to that of FDA review. For example, as a consultant I still think about things like technological characteristics, benefit/risk, and the appropriateness of predicate devices. I also frequently reference FDA Guidances and regulations, just as I did at FDA. In addition, I often change hats and “review” my draft submissions from the perspective of an FDA reviewer; this helps me to anticipate FDA questions and thereby strengthen the overall submission. So overall, writing a submission doesn’t feel too different from reviewing one.

Of course, there are some differences in consulting vs. FDA review. As a consultant at MCRA, I work on a larger range of project types than I did as an FDA reviewer. This includes both the types of devices and the types of work products. For example, at FDA, I worked only on cardiovascular devices without electrical components, also known as the “plumbing” devices. As a consultant with six months experience at MCRA, I have already worked on a larger range of technologies than I did at FDA, including cardiovascular, orthopedic, and wound care devices. Similarly, at FDA I mainly worked on US premarket reviews. As a consultant at MCRA, I do write US premarket submissions, but I also work on international submissions as well as developing overall regulatory strategy recommendations for clients, which consider not just the technology but also the regulatory time and costs of each potential pathway. I like the variety that comes with working as a consultant!


More about Robert Allen, PhD

For more information about Robert, please visit his LinkedIn page; and to learn more about MCRA, LLC, please visit their website.

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