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


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

Med Device Monday - XVIVO Perfusion System for Storing Human Organs Before Transplantation

Image from https://www.xvivoperfusion.com/products/xps/

Image from https://www.xvivoperfusion.com/products/xps/

An estimated 120,000 people in the U.S. are currently waiting for a life-saving organ transplant. Unfortunately, the demand for donated organs far outweighs their availability. Patients needing a lung transplant, for example, often wait months before an adequate lung or pair of lungs becomes available. Even with approximately 58% of Americans willing to donate their organs at the end of their life, the pool of donor lungs acceptable for transplantation is limited, either due to compatibility issues between the donor and the recipient, or issues related to the condition of the lung.

A recently approved device manufactured by XVIVO Perfusion, Inc. has the potential to increase the pool of donor lungs by allowing the safe transplantation of previously unacceptable organs. The XVIVO Perfusion System (XPS™) with STEEN Solution™ Perfusate is a machine that warms, flushes, preserves, and ventilates donated lungs for up to five (5) hours This allows the transplant team time to examine the lungs and evaluate their function. Perfusion, or the act of moving a liquid through the natural channels of an organ or tissue (in this case the donated lung or lungs), can allow for the safe transplantation of initially unacceptable organs because it:

(1) allows time for the lung(s) to re-establish their normal condition in an optimized environment,

(2) corrects physiologic problems caused by the buildup of fluid in the lung(s),

(3) dilutes and filters away any remaining donor blood and/or clots within the lung,

(4) supports re-expansion of collapsed portions of the lung(s), and

(5) allows time to assess and clean/suction residual and unwanted bronchial secretions.

The device consists of the XPS™ Perfusion Cart (both hardware and software), fluid path and non-fluid path disposables, and the STEEN Solution™, which is a clear, sterile, salt solution containing human serum albumin (HSA) and dextran 40. The system is designed to temporarily preserve and remove waste products from donor lung(s), helping maintain (and potentially improve) the condition of the donor lung tissue and giving the transplant team time to assess the lung(s) and whether they can be safely transplanted.

Interestingly, the XPS™ with STEEN Solution™ had previously secured FDA marketing authorization in 2014 via the humanitarian device exemption (HDE) regulatory pathway (H120003). The HDE is given to medical devices intended to benefit patients by treating or diagnosing diseases or conditions that affect less than 8,000 individuals in the United States per year. An HDE is exempt from the effectiveness requirements of Sections 514 and 515 of the FD&C Act, and is subject to certain profit and use restrictions. XVIVO Perfusion, Inc.’s current premarket approval (PMA) lifts the limit on annual patient use. This is an interesting and effective pathway for many devices that might be eligible for an HDE before they are ready to attack the full PMA process. Hopefully this device will continue to save lives as more lungs become available (and acceptable) for use!

Additional Reading:

  1. Device Approval Letter

  2. HDE Patient Information

  3. FDA Article

  4. HDE Description

  5. Company Website

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.


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

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.”