REGULATORY INTELLIGENCE

YEAR-END REPORT - 2021

Health Policy Tracking Service - Issue Briefs
Pharmaceuticals and Medical Devices
Medical Devices

This Issue Brief was written Robert S. White, a Compliance Attorney
on the publisher's editorial staff and a member of the Oklahoma bar.

12/20/2021
Il. FDA Device Approvals

FDA Authorizes Marketing of New Implant to Repair a Torn ACL

On December 16, 2020, the FDA granted marketing authorization-under the De Novo premarket review pathway-for an anterior
cruciate ligament (ACL) implant, intended to serve as an alternative to ACL reconstruction to treat ACL tears. The device, the Bridge-
Enhanced ACL Repair (BEAR) Implant, unlike traditional reconstruction, does not require the use of harvested tendons for ACL repair

and is the only currently- available alternative to reconstruction with allograft, autograft or suture-only repair for the treatment of ACL

rupture. [FN2]

'Torn ACLs are among the most common knee injuries in the U.S., but for years, treatment has been limited to ACL reconstruction,
which can be quite invasive and typically requires using tendon or a combination of tendon and bone from other parts of the body,
or obtained from a tissue bank, to complete the reconstruction," said Capt. Raquel Peat, Ph.D., MPH, USPHS, director of the Center
for Devices and Radiological Health's Office of Orthopedic Devices, 'Today's marketing authorization provides new options for the
hundreds of thousands of people affected by ACL rupture in the U.S. each year."

The ACL, a ligament stretching from the front to the back of the knee, aids in keeping the knee stable. Despite being a very common
injury, until today, the only surgical treatment available for tom ACLs has been ACL reconstruction using allograft, autograft or suture-
only repair.

The BEAR Implant is a resorbable implant-meaning it is absorbed by the body-made from bovine collagen and is secured via suture
to bridge the gap between the torn ends of a patient's ACL. The patient's own blood is injected into the implant during the surgical
implantation procedure with the intent of forming a device-protected clot that enables the body's healing process. Within about eight
weeks of the BEAR Implant surgical procedure, it is absorbed and replaced by the body's own tissue.

The FDA granted the marketing authorization to Miach Orthopaedics, Inc.
FDA Approves Prosthetic Implant for Above-the-Knee Amputations

On December 18, 2020, the FDA approved the Osseoanchored Prostheses for the Rehabilitation of Amputees (OPRA) Implant System,

the first implant system marketed in the U.S. for adults who have transfemoral-or above-the-knee-amputations and who have or are

anticipated to have rehabilitation problems with, or cannot use, a conventional socket prosthesis. [FNS]

'Today's approval of the OPRA Implant System expands options for prostheses for individuals who have had above-the-knee
amputations and can help those who have had or may have problems with rehabilitation and have not been able to benefit from
available socket prostheses," said Capt. Raquel Peat, Ph.D., MP.H., USPHS, director of the FDA's Center for Devices and Radiological
Health's Office of Orthopedic Devices. 'Prostheses can help people who have lost a leg due to trauma or cancer to regain mobility and
to more easily participate in everyday activities."

A conventional leg prosthesis uses a specially-fitted, cup-like shell called a socket that fits over the remaining portion of the patient's leg
(the residual limb remaining after amputation) to secure the device to the leg. Some patients may not have a long enough residual limb
to properly fit a socket prosthesis or may have other conditions, such as scarring, pain, recurrent skin infections or fluctuations in the

 
  

THOMSON REUTERS

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
shape of the residual limb that prevent them from being able to use a prosthesis with a socket. The OPRA Implant System is surgically
anchored and integrated into the patient's remaining thigh bone to allow connection to an external prosthetic limb.

The OPRA Implant System has been on the market under a humanitarian device exemption since 2015. Humanitarian use devices are
intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000
individuals in the U.S. per year.

The OPRA Implant System is manufactured by Integrum AB in M?Indal, Sweden.

FDA Releases Artificial Intelligence/Machine Learning Action Plan

On January 12, 2021, the FDA released the agency's first Artificial Intelligence/Machine Learning (Al/ML)-Based Software as a Medical
Device (SaMD) Action Plan IFN4] | This action plan describes a multi-pronged approach to advance the Agency's oversight of Al/ML-
based medical software. 'FNS!

This action plan describes a multi-pronged approach to advance the Agency's oversight of Al/ML-based medical software.

'This action plan outlines the FDA's next steps towards furthering oversight for Al/ML-based SaMD," said Bakul Patel, director of the
Digital Health Center of Excellence in the Center for Devices and Radiological Health (CDRH). 'The plan outlines a holistic approach
based on total product lifecycle oversight to further the enormous potential that these technologies have to improve patient care while
delivering safe and effective software functionality that improves the quality of care that patients receive. To stay current and address
patient safety and improve access to these promising technologies, we anticipate that this action plan will continue to evolve over time."

The Al/ML-Based Software as a Medical Device Action Plan outlines five actions that the FDA intends to take, including:

¢ Further developing the proposed regulatory framework, including through issuance of draft guidance on a predetermined change
control plan (for software's learning over time);

* Supporting the development of good machine learning practices to evaluate and improve machine learning algorithms;
* Fostering a patient-centered approach, including device transparency to users;

¢ Developing methods to evaluate and improve machine learning algorithms; and

¢ Advancing real-world performance monitoring pilots.

The Al/ML Action Plan is a response to stakeholder feedback received from the April 2019 discussion paper, Proposed Regulatory
Framework for Modifications to Artificial Intelligence/Machine Learning-Based Software as a Medical Device.

The FDA welcomes continued feedback in this area and looks forward to engaging with stakeholders on these efforts. The agency will
also continue to collaborate across the FDA to build a coordinated approach in areas of common focus related to Al/ML.

FDA Authorizes Marketing of Novel Device to Reduce Snoring and Mild Obstructive Sleep Apnea in Patients 18 Years and
Older

On February 8, 2021, the FDA authorized marketing of a new prescription only device intended to reduce snoring and mild obstructive
sleep apnea. Unlike devices used while patients sleep, this is the first device used while awake that is intended to improve tongue

muscle function, which in time can help prevent the tongue from collapsing backwards and obstructing the airway during sleep. [FN6]

'Obsiructive sleep apnea not only impacts sleep quality but can have other serious health impacts if untreated. Today's authorization
offers a new option for the thousands of individuals who experience snoring or mild sleep apnea," said Malvina Eydelman, MD., director
of the Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices in the FDA's Center for Devices and Radiological Health.

Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing with potential serious long-term effects. It can occur when
the upper airway becomes blocked repeatedly during sleep, reducing or completely stopping airflow. Untreated OSA can lead to
serious complications such as heart attack, glaucoma, diabetes, cancer and cognitive and behavioral disorders. OSA is categorized
by the number of apneas (pauses in breathing) plus the number of hypopneas (periods of shallow breathing) that occur, on average,
each hour. This number, called the Apnea-Hypopnea Index (AHI) measures the severity of OSA. Mild OSA is defined as an AHI
score of more than five but less than 15. The device, the eXciteOSA, is a removable tongue muscle stimulation device that delivers
neuromuscular stimulation to the tongue in order to reduce snoring and mild sleep apnea for patients who are 18 years or older.

The eXciteOSA device works by delivering electrical muscle stimulation through a mouthpiece that sits around the tongue. The
eXciteOSA mouthpiece has four electrodes, two located above the tongue and two located below the tongue. The device provides
electrical muscle stimulation action in sessions that consist of a series of electrical pulses with rest periods in between. It is used for 20
minutes once a day during a wakeful state, for a period of 6 weeks, and once a week thereafter.

The FDA granted the marketing authorization to Signifier Medical Technologies, LLC.
FDA Approves Implant for the Treatment of Rare Bone Disease as a Humanitarian Use Device

On February 17, 2021, the FDA approved the Patient Specific Talus Spacer 3D-printed talus implant for humanitarian use. The Patient
Specific Talus Spacer is the first in the world and first-of-its-kind implant to replace the talus-the bone in the ankle joint that connects

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
the leg and the foot-for the treatment of avascular necrosis (AVN) of the ankle joint, a serious and progressive condition that causes
the death of bone tissue stemming from a lack of blood supply to the area. The implant provides a joint-sparing alternative to other

surgical interventions commonly used in late-stage AVN that may disable motion of the ankle joint. [FN7]

'Avascular necrosis of the ankle, while a rare condition, is a serious and potentially debilitating one that causes pain and can lead to
inhibited motion of the ankle joint, and in some cases, removal of part of the leg," said Capt. Raquel Peat, Ph.D., M.P.H., USPHS,
director of the FDA's Center for Devices and Radiological Health's Office of Orthopedic Devices. 'Today's action provides patients with
a treatment option that could potentially reduce pain, retain range of motion of their joint and improve quality of life."

AVN is often caused by a sudden injury-such as a broken bone or a dislocated joint-or sustained damage to the tissue that develops
over time, and it occurs when there is a lack of blood supply to bone tissue, causing it to become necrotic, meaning it dies. When the
bones of a joint are affected, such as in the case of the ankle, the cartilage that keeps the bones from rubbing together can deteriorate,
causing arthritis and pain. Late-stage AVN of the ankle may result in the talus bone partially or fully collapsing. Current available
treatments include fusing the joints in the foot and ankle together-a procedure which helps to alleviate pain caused by AVN but
eliminates motion in the joint-or below-the-knee amputation.

The Patient Specific Talus Spacer is a 3D printed implant that can be used in talus replacement surgery. The talus spacer is made for
each patient individually, modeled from computed tomography (CT) imaging, and is fitted to a patient's specific anatomy. During the
replacement surgery, the patient's talus bone is removed and replaced with the implant, which is made from cobalt chromium alloy.

While fusion may become necessary in the future should the condition worsen, talus replacement surgery with the Patient Specific
Talus Spacer is intended to be a joint-sparing procedure, as it allows the patient to retain motion in the ankle joint.

The FDA granted the HDE approval of the Patient Specific Talus Spacer to Additive Orthopaedics, LLC.
FDA Authorizes Marketing of Novel Device to Help Protect Athletes' Brains During Head Impacts

On February 26, 2021, the FDA authorized marketing of a new device intended to be worn around the neck of athletes aged 13 years
and older during sports activities to aid in the protection of the brain from the effects associated with repetitive sub-concussive head
impacts. The non-invasive device, called Q-Collar, is a C-shaped collar that applies compressive force to the neck and increases blood
volume to help reduce movement of the brain within the cranial space which may occur during head impacts. The device may reduce

the occurrence of specific changes in the brain that are associated with brain injury. [FN8]

'Today's action provides an additional piece of protective equipment athletes can wear when playing sports to help protect their

brains from the effects of repetitive head impacts while still wearing the personal protective equipment associated with the sport," said
Christopher M. Loftus, M.D., acting director of the Office of Neurological and Physical Medicine Devices in the FDA's Center for Devices
and Radiological Health.

Traumatic brain injury (TBI) can be caused by a forceful bump, blow, or jolt to the head or body, or from an object that pierces the skull
and enters the brain. Not all blows or jolts to the head result in a TBI. According to the Centers for Disease Control and Prevention,
from 2006 to 2014, the number of TBl-related emergency department visits, hospitalizations, and deaths increased by 53%. Blunt
trauma accidents, or accidents that involve being struck by or against an object, particularly sports-related injuries, are a major cause
of TBI. The National Institute of Neurological Disorders and Stroke notes that anywhere from 1.6 million to 3.8 million sports- and
recreation-related TBls are estimated to occur in the United States annually.

When worn around the neck during sports activities, the Q-Collar provides compressive force to the internal jugular veins, which in turn
increases the blood volume in the skull's blood vessels. Typically, when people experience blunt trauma accidents, the brain moves
unrestrained in the skull, which is known as a 'slosh." The Q-Collar's increase in blood volume in those blood vessels creates a tighter
fit of the brain inside the skull and reduces the 'slosh' movement. By reducing the movement of the brain within the cranial space, the
Q-Collar may aid in the protection of the brain from the effects of head impacts.

The FDA granted marketing authorization of the Q-Collar to Q30 Sports Science, LLC.
FDA Authorizes First Robotically-Assisted Surgical Device for Performing Transvaginal Hysterectomy

On March 1, 2021, the FDA authorized marketing of the Hominis Surgical System, a new robotically-assisted surgical device (RASD)
that can help facilitate transvaginal hysterectomy in certain patients. The Hominis Surgical System is intended for benign hysterectomy

(removal of the uterus for non-cancerous conditions) with salpingo-oophorectomy (removal of one or both fallopian tubes and ovaries).
[FNQ]

'We are providing physicians and patients another minimally-invasive gynecologic surgical option for non-cancerous conditions," said
Binita Ashar, M.D., MBA, FACS, director of the Office of Surgical and Infection Control Devices in the FDA's Center for Devices and
Radiological Health. 'The FDA continues to support advancements in safe and effective medical devices that can improve patient
experiences when undergoing surgical procedures."

RASD, sometimes referred to as robotic surgical devices or computer-assisted surgical devices, are not actually robots. The devices
cannot perform surgery without direct human control. RASD enable a surgeon to use computer and software technology to control
and move surgical instruments through one or more tiny ports (incisions or orifices) in the patient's body and in a variety of surgical

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
procedures or operations. RASD technology facilitates performing minimally-invasive surgery and complex tasks in confined areas
inside the body.

To remove the uterus, the Hominis Surgical System uses minimally-invasive surgical instruments inserted through the vagina
(transvaginal approach) and a video camera inserted laparoscopically through a small incision on the abdomen for visualization of
the instruments inside the patient. The transvaginal approach requires fewer incisions on the abdomen compared to conventional
laparoscopic hysterectomy. During the procedure, surgeons in the operating room control the instruments from the Hominis Surgical
System console. The FDA will require the manufacturer to develop and provide a comprehensive training program for surgeons and
operating room staff to complete before operation of the device.

The FDA granted marketing authorization of the Hominis Surgical System to Memic Innovative Surgery Ltd.
FDA Permits Marketing of First SARS-CoV-2 Diagnostic Test Using Traditional Premarket Review Process

On March 17, 2021, the FDA granted marketing authorization of the BioFire Respiratory Panel 2.1 (RP2.1), a diagnostic test for the
simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs
(NPS) obtained from individuals suspected of COVID-19 and other respiratory tract infections. The diagnostic test, which had an
Emergency Use Authorization (EUA), was granted marketing authorization using the De Novo premarket review pathway, a regulatory
pathway for low- to moderate-risk devices of a new type. The grant of this De Novo request marks an important step in FDA's response
to the COVID-19 pandemic because it is the first SARS-CoV-2 diagnostic test that will be permitted to be marketed beyond the public

health emergency. [FN 10]

'Today's action is a great demonstration of the FDA's work to protect the public health in emergency response situations and
beyond," said FDA Acting Commissioner Janet Woodcock, M.D. 'We ensured there were tests made available quickly under EUA;
and we continue to work with diagnostic manufacturers to take the next step of ensuring products are FDA reviewed for safety and
effectiveness and authorized for marketing under our traditional premarket authorities. While this is the first marketing authorization
for a diagnostic test using a traditional premarket review process, we do not expect this to be the last and look forward to working with
developers of medical products to move their products through our traditional review pathways."

The FDA granted the marketing authorization to BioFire Diagnostics LLC.
FDA Approves First in the World Device to Treat Patients with Congenital Heart Disease

On March 26, 2021, the FDA approved the first in the world non-surgical heart valve to treat pediatric and adult patients with a native
or surgically-repaired right ventricular outflow tract (RVOT), the part of the heart that carries blood out of the right ventricle to the
lungs. The device is designed for patients who have severe pulmonary valve regurgitation (blood leaking backward into the right lower
chamber of the heart), a condition that often results from congenital heart disease. The device, called the Harmony Transcatheter
Pulmonary Valve (TPV) System, is intended to improve blood flow to the lungs in patients with severe pulmonary valve regurgitation
without open-heart surgery, which is the current standard of care. The use of the Harmony valve may delay the time before a

patient needs additional open-heart surgery. It can also potentially reduce the total number of open-heart surgeries required over an

individual's lifetime. ~\™!

'The Harmony TPV provides a new treatment option for adult and pediatric patients with certain types of congenital heart disease. It
offers a less-invasive treatment alternative to open-heart surgery to patients with a leaky native or surgically-repaired RVOT and may
help patients improve their quality of life and return to their normal activities more quickly, thus fulfilling an unmet clinical need of many
patients with congenital heart disease," said Bram Zuckerman, M.D., director of the Office of Cardiovascular Devices in the FDA's
Center for Devices and Radiological Health.

Congenital heart defects (CHDs) are conditions that are present at birth and can affect the structure of a baby's heart and the way

it works. They are the most common type of birth defect, affecting about 40,000 babies born each year. It is estimated that over two
million infants, children, adolescents and adults are living with CHDs in the U.S. Patients with CHDs often require heart procedures
early in life to help improve blood flow to the lungs. After having one of these procedures, the patient may or may not have a working
pulmonary valve, which could lead to pulmonary regurgitation. Severe pulmonary valve regurgitation may be corrected through open-
heart surgery to place a right ventricle-pulmonary artery conduit or an artificial valve.

During the implantation procedure of a Harmony valve, a thin, hollow tube (catheter) with a collapsed Harmony valve on the end is
inserted through a vein in the groin or in the neck and into the right side of the heart, and then into the RVOT where it is placed into
position. The valve is then released from the catheter; it expands on its own, and anchors to the RVOT. Once the new valve is in place,
it opens and closes like a door to force the blood to flow in the correct direction.

FDA Authorizes Marketing of Device to Improve Gait in Multiple Sclerosis Patients

On March 26, 2021, the FDA authorized marketing of a new device indicated for use as a short-term treatment of gait deficit due to
mild to moderate symptoms from multiple sclerosis (MS). The device is intended to be used by prescription only as an adjunct to a
supervised therapeutic exercise program in patients 22 years of age and older. The device, called Portable Neuromodulation Stimulator

(PoNS), is a neuromuscular tongue stimulator that consists of a non-implantable apparatus to generate electrical pulses for stimulation

of the trigeminal and facial nerves via the tongue to provide treatment of motor deficits. [FN12]

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
'MS is one of the most common neurological diseases in young adults. Today's authorization offers a valuable new aid in physical
therapy and increases the value of additional therapies for those who live with MS on a daily basis," said Christopher M. Loftus, M.D.,
acting director of the Office of Neurological and Physical Medicine Devices in the FDA's Center for Devices and Radiological Health.

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communications between the brain

and other parts of the body. According to the National Institute of Neurological Disorders and Stroke, most people experience their first
symptoms of MS between the ages of 20 and 40 and the disease occurs more frequently in women than in men. MS is a disease that
affects people differently as it causes a variety of symptoms-such as problems with walking and balance-that can interfere with daily
activities but can usually be treated or managed. The most common walking problem is unsteady, uncoordinated movements (known
as ataxia) due to damage to the areas of the brain that coordinate muscle balance. People with severe ataxia generally benefit from the
use of a cane, walker, or other assistive device. Physical therapy can also reduce walking problems.

The PoNS device is a portable, non-implantable device which delivers mild neuromuscular electrical stimulation to the dorsal surface
of the patient's tongue. It consists of a controller and a mouthpiece that are connected to each other by a cord. The mouthpiece is held
lightly in place by the lips and teeth and the control unit is worn around the neck during a patient's visit with a therapist. The controller
sends signals to the mouthpiece placed on the tongue; receptors on the tongue send millions of neural impulses to the brain through
natural pathways. Additionally, the therapist can connect the control unit to a computer and view usage data via software developed
specifically for the PONS device. The usage data gives the therapist information on how to improve a patient's execution of therapy by
identifying potential areas of missed or shortened sessions.

The FDA granted marketing authorization of the Portable Neuromodulation Stimulator to Helius Medical, Inc.
FDA Authorizes Marketing of First Device that Uses Artificial Intelligence to Help Detect Potential Signs of Colon Cancer

On April 9, 2021, the FDA authorized marketing of the GI Genius, the first device that uses artificial intelligence (Al) based on machine

learning to assist clinicians in detecting lesions (such as polyps or suspected tumors) in the colon in real time during a colonoscopy.
[FN13]

'Artificial intelligence has the potential to transform health care to better assist health care providers and improve patient care. When Al
is combined with traditional screenings or surveillance methods, it could help find problems early on, when they may be easier to treat,"
said Courtney H. Lias, Ph.D. acting director of the GastroRenal, ObGyn, General Hospital and Urology Devices Office in the FDA's
Center for Devices and Radiological Health. 'Studies show that during colorectal cancer screenings, missed lesions can be a problem
even for well-trained clinicians. With the FDA's authorization of this device today, clinicians now have a tool that could help improve
their ability to detect gastrointestinal lesions they may have missed otherwise."

According to the National Institutes of Health, colorectal cancer is the third leading cause of death from cancer in the United States.
Colorectal cancer usually starts from polyps or other precancerous growths in the rectum or the colon (large intestine). As part of a
colorectal cancer screening and surveillance plan, clinicians perform colonoscopies to detect changes or abnormalities in the lining of
the colon and rectum. A colonoscopy involves threading an endoscope (thin, flexible tube with a camera at the end), through the rectum
and throughout the entire length of the colon, allowing a clinician to see signs of cancer or precancerous lesions.

The GI Genius is composed of hardware and software designed to highlight portions of the colon where the device detects a potential
lesion. The software uses artificial intelligence algorithm techniques to identify regions of interest. During a colonoscopy, the GI Genius
system generates markers, which look like green squares and are accompanied by a short, low-volume sound, and superimposes them
on the video from the endoscope camera when it identifies a potential lesion. These signs signal to the clinician that further assessment
may be needed, such as a closer visual inspection, tissue sampling, testing or removal, or ablation of (burning) the lesion. The Gl
Genius is designed to be compatible with many FDA-cleared standard video endoscopy systems.

The FDA granted marketing authorization of the GI Genius to Cosmo Artificial Intelligence, Ltd.
FDA Authorizes Marketing of Device to Facilitate Muscle Rehabilitation in Stroke Patients

On April 23, 2021, the FDA authorized marketing of a new device indicated for use in patients 18 and older undergoing stroke
rehabilitation to facilitate muscle re-education and for maintaining or increasing range of motion. The Neurolutions IpsiHand Upper
Extremity Rehabilitation System (IpsiHand System) is a Brain-Computer-Interface (BCI) device that assists in rehabilitation for stroke

patients with upper extremity-or hand, wrist and arm-disability. [FN14]

'Thousands of stroke survivors require rehabilitation each year. Today's authorization offers certain chronic stroke patients undergoing
stroke rehabilitation an additional treatment option to help them move their hands and arms again and fills an unmet need for patients
who may not have access to home-based stroke rehabilitation technologies," said Christopher M. Loftus, M.D., acting director of the
Office of Neurological and Physical Medicine Devices in the FDA's Center for Devices and Radiological Health.

A stroke occurs when normal blood flow to the brain is interrupted. Brain cells obtain oxygen and nutrients from regular blood
circulation, so when there is a blockage of blood flow to the brain caused by a clot (an ischemic stroke) or excessive bleeding in the
brain due to a ruptured blood vessel (a hemorrhagic stroke), the brain cells can die from a lack of blood and oxygen. Although stroke

is a brain disease, it can affect the entire body and sometimes causes long-term disability such as complete paralysis of one side of
the body (hemiplegia) or one-sided weakness (hemiparesis) of the body. Stroke survivors may have problems with the simplest of daily

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
activities, including speaking, walking, dressing, eating and using the bathroom. According to the Centers for Disease Control and
Prevention, someone in the United States has a stroke every 40 seconds. About 795,000 people in the U.S. have a stroke each year.

Post-stroke rehabilitation helps individuals overcome disabilities that result from stroke damage. The IpsiHand System uses non-
invasive electroencephalography (EEG) electrodes instead of using an implanted electrode or other invasive feature to record brain
activity. The EEG data is then wirelessly conveyed to a tablet for analysis of the intended muscle movement (intended motor function)
and a signal is sent to a wireless electronic hand brace, which in turn moves the patient's hand. The device aims to help stroke patients
improve grasping. The device is prescription-only and may be used as part of rehabilitation therapy.

The FDA granted marketing authorization of the Neurolutions IpsiHand Upper Extremity Rehabilitation System to Neurolutions, Inc.
FDA Authorizes Marketing of Diagnostic Aid for Autism Spectrum Disorder

On June 2, 2021, the FDA authorized marketing of a device to help diagnose autism spectrum disorder (ASD). The Cognoa ASD
Diagnosis Aid is a machine learning-based software intended to help health care providers diagnose ASD in children 18 months

through 5 years of age who exhibit potential symptoms of the disorder. [FN15]

'Autism spectrum disorder can delay a child's physical, cognitive and social development, including motor skill development, learning,
communication and interacting with others. The earlier ASD can be diagnosed, the more quickly intervention strategies and appropriate
therapies can begin," said Jeff Shuren, M.D., J.D., director of the FDA's Center for Devices and Radiological Health. 'Today's marketing
authorization provides a new tool for helping diagnose children with ASD."

The Centers for Disease Control and Prevention defines ASD as a 'developmental disability that can cause significant social,
communication and behavioral challenges" and is estimated to affect about 1 in 54 children. Because ASD symptoms can vary greatly,
the disorder may be difficult to diagnose. While ASD may be detected as early as 18 months old, many children are not diagnosed until
later in childhood, which can delay treatment and early intervention. The average age of diagnosis for ASD is 4.3 years. Some delays in
diagnosis are due to the need for children to be referred to specialists with expertise in ASD.

The Cognoa ASD Diagnosis Aid is a software as a medical device that uses a machine learning algorithm to receive input from parents
or caregivers, video analysts and health care providers to assist physicians evaluate a patient at risk of ASD. The device consists of
three main components: a mobile app for caregivers and parents to answer questions about behavior problems and to upload videos
of their child; a video analysis portal that allows manufacturer-trained and certified specialists to view and analyze uploaded videos of
patients; and a health care provider portal that is intended for a health care provider to enter answers to pre-loaded questions about
behavior problems, track the information provided by parents or caregivers and review a report of the results. After processing the
information provided by parents, caregivers and healthcare providers, the ASD Diagnosis Aid reports a positive or negative diagnosis
if there is sufficient information for its algorithm to make a diagnosis. If there is insufficient information to render a 'Positive for ASD" or
'Negative for ASD' result to help determine a diagnosis, the ASD Diagnosis Aid will report that no result can be generated.

The FDA granted the marketing authorization to Cognoa, Inc.
FDA Approves First-of-lts-Kind Stroke Rehabilitation System

On August 27, 2021, the FDA approved the MicroTransponder Vivistim Paired VNS System (Vivistim System), a first-of-its-kind, drug-
free rehabilitation system intended to treat moderate to severe upper extremity motor deficits associated with chronic ischemic stroke-

a stroke caused by a blockage of blood flow to the brain with long-lasting symptoms-using vagus nerve stimulation (VNS). [FN16]

'People who have lost mobility in their hands and arms due to ischemic stroke are often limited in their treatment options for regaining
motor function" said Christopher M. Loftus, M.D., acting director of the FDA's Center for Devices and Radiological Health's Office of
Neurological and Physical Medicine Devices. 'Today's approval of the Vivistim Paired VNS System offers the first stroke rehabilitation
option using vagus nerve stimulation. Used alongside rehabilitative exercise, this device may offer benefit to those who have lost
function in their upper limbs due to ischemic stroke."

A stroke occurs when blood flow to part of the brain is interrupted, causing brain cells to die from a lack of oxygen and nutrients
contained in the blood. There are different types of stroke, but the most common type is ischemic stroke, meaning the blood vessels to
the brain become clogged, which blocks blood flow from reaching the brain. Depending on how long the brain is deprived of blood and
where in the brain the stroke occurs, stroke can lead to brain damage, temporary or permanent disabilities, and in some cases, death.
Disabilities resulting from stroke may include, but are not limited to, total or partial paralysis or difficulty with muscle movement.

The Vivistim System is intended to be used, along with post-stroke rehabilitation therapy, in patients who have had ischemic stroke,

to electrically stimulate the vagus nerve-a nerve that runs from the brain down to the abdomen-to reduce deficiencies in upper limb
and extremity motor function and to improve patients' ability to move their arms and hands. To use the Vivistim System, an implantable
pulse generator (IPG}-which generates a mild electrical pulse-is implanted just under the skin in the chest of the patient. Attached to
the IPG is a lead wire that is implanted under the skin and leads up to electrodes that are placed on the left side of the neck where the
vagus nerve is.

Accompanying the implantable components are clinician software preloaded onto a laptop and a wireless transmitter to be used only by
a health care provider. The software allows a health care provider managing a patient's rehabilitation to input the appropriate settings

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
on the IPG, including amplitude, frequency, and pulse width for the stimulation, and also records stimulation history, movements
performed, and information about the IPG. The wireless transmitter communicates adjustments to the IPG settings made using the
software.

The MicroTransponder Vivistim Paired VNS System is manufactured by MicroTransponder Inc.
FDA Authorizes Software that Can Help Identify Prostate Cancer

On September 21, 2021, the FDA authorized marketing of software to assist medical professionals who examine body tissues
(pathologists) in the detection of areas that are suspicious for cancer as an adjunct (supplement) to the review of digitally-scanned slide
images from prostate biopsies (tissue removed from the body). The software, called Paige Prostate, is the first artificial intelligence (Al)-

based software designed to identify an area of interest on the prostate biopsy image with the highest likelihood of harboring cancer so it

can be reviewed further by the pathologist if the area of concern has not been identified on initial review. [FN17]

'Pathologists examine biopsies of tissue suspected for diseases, such as prostate cancer, every day. Identifying areas of concern

on the biopsy image can help pathologists make a diagnosis that informs the appropriate treatment," said Tim Stenzel, M.D., Ph.D.,
director of the Office of In Vitro Diagnostics and Radiological Health in the FDA's Center for Devices and Radiological Health. 'The
authorization of this Al-based software can help increase the number of identified prostate biopsy samples with cancerous tissue, which
can ultimately save lives."

Cancer that starts in the prostate is called prostate cancer. According to the Centers for Disease Control and Prevention, aside from
non-melanoma skin cancer, prostate cancer is the most common cancer among men in the United States. It is also one of the leading
causes of cancer death among men.

Paige Prostate is compatible for use with slide images that have been digitized using a scanner. The digitized slide image can then be
visualized using a slide image viewer.

The FDA granted marketing authorization of the Paige Prostate software to Paige.Al.

FDA Clears First Major Imaging Device Advancement for Computed Tomography

On September 30, 2021, the FDA cleared the first new major technological improvement for Computed Tomography (CT) imaging in
nearly a decade. [FN'18]

'Computed tomography is an important medical imaging tool that can aid in diagnosing disease, trauma or abnormality; planning

and guiding interventional or therapeutic procedures; and monitoring the effectiveness of certain therapies," said Laurel Burk, Ph.D.,
assistant director of the Diagnostic X-ray Systems Team in the FDA's Center for Devices and Radiological Health. 'Today's action
represents the first major new technology for computed tomography imaging in nearly a decade and underscores the FDA's efforts to
encourage innovation in areas of scientific and diagnostic progress."

The device uses the emerging CT technology of photon-counting detectors which can measure each individual X-ray that passes
through a patient's body, as opposed to current systems which use detectors that measure the total energy contained in many X-rays
at once. By "counting' each individual X-ray photon, more detailed information about the patient can be obtained and used to create
images with less information that is not useful in the review and analysis.

Computed tomography (sometimes called computerized tomography) is a noninvasive medical examination or procedure that uses
specialized X-ray equipment to produce cross-sectional images of the body. Each cross-sectional image represents a "slice' of the
person being imaged, not unlike the slices in a loaf of bread. These cross-sectional images are used for a variety of diagnostic and
therapeutic purposes.

CT scans can be performed on every region of the body for a variety of reasons. The CT system then converts these counts or
measurements through complex software into the recorded images the health care provider reads and analyzes.

The new diagnostic imaging device, called Siemens NAEOTOM Alpha, is designed to transform the information from X-ray photons that
pass through a patient's body, and are received by a detector, into a detailed 3-dimensional image. The images delivered by the system
can be used by a trained physician as an aid in diagnosis or can be used by trained staff as an aid in diagnosis, treatment preparation
and radiation therapy planning.

The FDA granted clearance of Siemens NAEOTOM Alpha to Siemens Medical Solutions Inc.
FDA Issues Proposal to Improve Access to Hearing Aid Technology
On October 19, 2021, the FDA issued a proposal intended to improve access to and reduce the cost of hearing aid technology for

millions of Americans. The agency proposed a rule IFN19] to establish a new category of over-the-counter (OTC) hearing aids. When
finalized, the rule would allow hearing aids within this category to be sold directly to consumers in stores or online without a medical
exam or a fitting by an audiologist. The proposed rule is designed to help increase competition in the market while also ensuring the

safety and effectiveness of OTC and prescription hearing aids. [FN20]

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
This action follows President Biden's July Executive Order [FN21] on Promoting Competition in the American Economy, which called for

the FDA to take steps to allow hearing aids to be sold over the counter. This effort also builds on the Biden-Harris Administration's goal
of expanding access to high-quality health care and lowering medical care costs for the American public.

'Reducing health care costs for everyone in America is a top priority," said Health and Human Services Secretary Xavier Becerra.
'Today's move by FDA takes us one step closer to the goal of making hearing aids more accessible and affordable for the tens of
millions of people who experience mild to moderate hearing loss."

The proposed rule would amend existing rules that apply to hearing aids for consistency with the new OTC category, repeal the
conditions for sale for hearing aids and address state regulation of hearing aids. The OTC category, when finalized, would apply to
certain air-conduction hearing aids intended for adults age 18 and older who have perceived mild to moderate hearing loss. Hearing
aids for severe hearing loss or for users younger than age 18 would be prescription devices.

To coincide with the proposed rule, the FDA also issued an updated draft guidance, Regulatory Requirements for Hearing Aid Devices
and Personal Sound Amplification Products (PSAPs). The draft guidance describes hearing aids, PSAPs, their respective intended
uses and regulatory requirements that apply to both types of products. The draft guidance is intended to provide further clarification
regarding the differences between PSAPs, which help people with normal hearing amplify sounds, and hearing aids and to inform
consumers that PSAPs are not considered OTC alternatives for hearing aids.

FDA Strengthens Safety Requirements and Updates Study Results for Breast Implants

On October 27, 2021, the FDA took several new actions to strengthen breast implant risk communication and help those who are

considering breast implants make informed decisions. [FN22]

First, the agency issued orders restricting the sale and distribution of breast implants to help ensure that patients considering breast
implants are provided with adequate risk information so that they can make fully informed decisions. Additionally, the agency has
approved new labeling for all legally marketed breast implants that includes a boxed warning, a patient decision checklist, updated
silicone gel-filled breast implant rupture screening recommendations, a device description with a list of specific materials used in

the device and a patient device card. Finally, the FDA released updated information on the status of breast implant manufacturer
post-approval studies. These actions will help patients understand the risks and benefits of breast implants and make more informed
decisions about their health.

'Protecting patients' health when they are treated with a medical device is our most important priority," said Binita Ashar, M.D., director
of the Office of Surgical and Infection Control Devices in the Center for Devices and Radiological Health. 'In recent years, the FDA has
sought more ways to increase patients' access to clear and understandable information about the benefits and risks of breast implants.
By strengthening the safety requirements for manufacturers, the FDA is working to close information gaps for anyone who may be
considering breast implant surgery. As the FDA continues to evaluate the overall effects of breast implants in patients, today's actions
help ensure that all patients receive the information they need to make well-informed decisions affecting their long-term, personal
health."

The FDA's order restricts the sale and distribution of breast implants to only health care providers and facilities that provide information
to patients utilizing the patient brochure 'Patient Decision Checklist." The checklist must be reviewed with the prospective patient

by the health care provider to help ensure the patient understands the risks, benefits and other information about the breast implant
device. The patient must be given the opportunity to initial and sign the patient decision checklist and it must be signed by the physician
implanting the device.

The FDA is requiring these restrictions based on its finding that the available information indicates such restrictions are necessary to
provide a reasonable assurance of the device's safety and effectiveness. The FDA is committed to continuing to use its full authorities
to ensure the post-market safety of medical products.

Breast implants are designated as a Class III medical device, which includes devices that support or sustain human life, are of
substantial importance in preventing impairment of human health or which present a potential, unreasonable risk of illness or injury.
Due to the level of risk associated, Class III devices require PMA approval before a manufacturer can legally market their device, which
is the most stringent type of device marketing application required by the FDA.

FDA Authorizes Marketing of Virtual Reality System for Chronic Pain Reduction

On November 16, 2021, the FDA authorized marketing of EaseVRx, a prescription-use immersive virtual reality (VR) system that

uses cognitive behavioral therapy and other behavioral methods to help with pain reduction in patients 18 years of age and older with
diagnosed chronic lower back pain. [FN23]

'Millions of adults in the United States are living with chronic lower back pain that can affect multiple aspects of their daily life," said
Christopher M. Loftus, M.D., acting director of the Office of Neurological and Physical Medicine Devices in the FDA's Center for Devices
and Radiological Health. 'Pain reduction is a crucial component of living with chronic lower back pain. Today's authorization offers a

treatment option for pain reduction that does not include opioid pain medications when used alongside other treatment methods for
chronic lower back pain."

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
Chronic lower back pain, which is defined as moderate to severe pain in the lower back lasting longer than three months, is one of the
most common chronic pain conditions in the U.S. Chronic pain may inhibit mobility or daily activities and has been linked to anxiety
and depression, poor perceived health or reduced quality of life and dependence on opioids. Current treatment plans for chronic lower
back pain often include, among other options, prescription and over-the-counter pain medications, exercise, steroid injections, surgery
and transcutaneous electrical nerve stimulation. Cognitive behavioral therapy (CBT) may be used to reduce the burden of chronic pain
and increase function through an emotional, cognitive and behavioral approach to shift negative beliefs held by patients about the
relationship between their pain and movement.

EaseVRx employs the principles of CBT and other behavioral therapy techniques for the purpose of reduction of pain and pain
interference. The prescription device, which is intended for at-home self-use, consists of a VR headset and a controller, along with a
'Breathing Amplifier' attached to the headset that directs a patient's breath toward the headset's microphone for use in deep breathing
exercises. The device's VR program uses established principles of behavioral therapy intended to address the physiological symptoms
of pain and aid in pain relief through a skills-based treatment program. These principles include deep relaxation, attention-shifting,
interoceptive awareness?the ability to identify, access, understand and respond appropriately to the patterns of internal signals-and
perspective-taking, distraction, immersive enjoyment, self-compassion, healthy movement, acceptance, visualization, knowledge of
pain and rehabilitation.

The EaseVRx treatment program consists of 56 VR sessions that are 2-16 minutes in length, which are intended to be used as part of a
daily eight-week treatment program. Each session incorporates elements of the aforementioned principles to provide the user with skills
to achieve relief and reduction in the interference of pain in daily activities.

EaseVRx is manufactured by AppliedVR
ll. Warnings, Recalls and Suspensions

FDA Warns Pulse oximeters should not be used to diagnose COVID-19

On February 19, 2021, the FDA issued a warning [FN24] regarding the use of pulse oximeters. The warning indicated that the

Coronavirus Disease 2019 (COVID-19) pandemic has caused an increase in the use of pulse oximeters, and a recent report [FN25]

( Sjoding et al. ) suggests that the devices may be less accurate in people with dark skin pigmentation. The FDA is informing patients
and health care providers that although pulse oximetry is useful for estimating blood oxygen levels, pulse oximeters have limitations
and a risk of inaccuracy under certain circumstances that should be considered. Patients with conditions such as COVID-19 who
monitor their condition at home should pay attention to all signs and symptoms of their condition and communicate any concerns to
their health care provider.

FDA Warns that Magnets in Cell Phones and Smart Watches May Affect Pacemakers and Other Implanted Medical Devices

On May 13, 2021, the FDA issued a notice advising the public that some newer consumer electronic devices such as certain cell

phones and smart watches, have high field strength magnets capable of placing medical devices in their 'magnet mode." These

magnets can affect normal operations of the medical device until the magnetic field is moved. [FN26]

Many implanted medical devices are designed with a 'magnet mode" to allow for safe operation during certain medical procedures such
as undergoing an MRI scan. These safety features are typically engaged by physicians with the use of a high field strength magnet
that is placed near the implanted device placing it into a 'magnet mode." Removal of the magnetic field causes the device to return to
normal operation.

The FDA recommends patients keep any consumer electronic devices that may create magnetic interference, including cell phones and
smart watches, at least six inches away from implanted medical devices, in particular cardiac defibrillators. Many implanted medical
devices have FDA-approved information written for patients (patient labeling), which cautions patients to keep all cell phones and smart
watches at least six inches from the implanted medical device.

FDA Alerts Health Care Providers to Stop New Implants of Certain Ventricular Assist Device System

On June 3, 2021, the FDA issued an alert IFN27] to health care providers to no longer implant end-stage heart failure patients with
Medtronic's Heartware Ventricular Assist Device (HVAD) System due to a growing body of observational clinical comparisons that
demonstrates a higher frequency of neurological adverse events and mortality associated with the system when compared to other
commercially available devices, as well as complaints that the internal pump may delay or fail to restart.

Medtronic is stopping the distribution and sale of the HVAD System and has issued an Urgent Medical Device Communication
Notification Letter requesting physicians to stop new implants of the device. This action comes after the company received over 100
complaints involving delay or failure to restart of the HVAD pump, including reports of 14 patient deaths and 13 cases where an
explant was necessary. According to Medtronic, there are approximately 2,000 patients in the U.S. implanted with the device and 4,000
worldwide.

Ill. Other Developments

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
FDA Announces Draft Guidances to Help Increase Transparency, Assist Reporting and Timely Completion for Certain Medical
Device Studies after FDA Approval or Clearance

On May 26, 2021, the FDA issued two guidances regarding the surveillance of certain medical devices. The following quote is attributed
to William Maisel, M.D., chief medical officer and director of the Office of Product Evaluation and Quality in FDA's Center for Devices

and Radiological Health: N28!

'Today, the FDA issued two draft guidance documents regarding the continuous surveillance of certain FDA approved and cleared
devices. When final, these guidance documents will help increase transparency and assist reporting and timely completion of studies
on the safety and effectiveness of certain devices.

Even after a device receives FDA clearance or approval to be marketed, our regulatory role continues. We receive and review
additional data on certain devices to inform our oversight for the safe and effective use of a device throughout the device lifecycle.
These draft guidance documents describing postmarket surveillance of moderate and high-risk devices and post-approval study
procedures provide clarity that will help manufacturers better understand the FDA's requirements and expectations for ongoing data
collection for certain approved or cleared devices, which we believe will help increase reporting compliance.

The FDA will continue to reinforce to device sponsors the importance of engaging early and often with the agency to ensure data are
properly collected and that all required postmarket studies are properly implemented. Our commitment is to protect the public health by
ensuring that devices on the market continue to be safe and effective. FDA's review of data from post-approval studies and postmarket
surveillance is an important part of that commitment.'

The first guidance on postmarket surveillance guidance IFN29] will assist manufacturers of devices subject to an order under section 522

of the Federal Food, Drug, and Cosmetic Act, which authorizes the FDA to require postmarket surveillance (522 order) at any time in
the lifecycle of certain Class II (moderate risk) and III (high risk) devices that meet any of the following criteria: a failure with the device
would be reasonably likely to have a serious adverse health consequence; the device is expected to be used significantly in pediatric
populations; the device is intended to be implanted in the human body for more than one year or a device that is intended to be life-
sustaining; or life-supporting and used outside of a device user facility.

The second guidance is an updated post-approval study guidance [FN30] that will assist stakeholders with understanding post-approval
study requirements imposed as a condition of PMA approval by providing procedural information, recommendations conceming post-
approval related submissions and other.

FDA Revokes Emergency Use Authorizations for Certain Respirators and Decontamination Systems as Access to N95s
Increases Nationwide

On June 30, 2021, the FDA announced it is revoking EUAs of all non-NIOSH (National Institute of Occupational Safety and Health)-
approved disposable respirators, which includes imported disposable respirators such as KN95s, along with revoking EUAs for
decontamination and bioburden reduction systems.

The following quote is attributed to Suzanne Schwartz, M.D., M.B.A., director of the Office of Strategic Partnerships and Technology
Innovation in the FDA's Center for Devices and Radiological Health:

'Throughout the pandemic, the FDA has worked closely with our federal partners at the Centers for Disease Control and Prevention's
National Institute for Occupational Safety and Health (NIOSH), the Occupational Safety and Health Administration (OSHA) and with
manufacturers to protect our front-line workers by facilitating access to the medical supplies they require. As a result of these efforts,
our country is now better positioned to provide health care workers with access to NIOSH-approved N95s rather than using non-
NIOSH-approved respirators or reusing decontaminated disposable respirators.

Early in the public health emergency, there was a need to issue emergency use authorizations (EUAs) for non-NIOSH-approved
respirators as well as decontamination and bioburden reduction systems to disinfect disposable respirators. Today, those conditions no
longer exist. Our national supply of NIOSH-approved N95s is more accessible to our health care workers every day.

Today, the FDA is taking additional action by announcing the revocation of EUAs for imported, non-NIOSH-approved respirators as well
as decontamination and bioburden reduction systems because of an increase in domestically-manufactured NIOSH-approved N95s
available throughout the country. As access to domestic supply of disposable respirators continues to significantly improve, health care
organizations should transition away from crisis capacity conservation strategies that were implemented at the onset of the pandemic."

Bipartisan Legislation Introduced Promising Patient Access to Breakthrough Medical Products

On June 23, 2021, the Ensuring Patient Access to Critical Breakthrough Products Act '"N3"! (2021 CONG US HR 4043) was introduced
by Representatives Suzan DelBene (WA-01), Jackie Walorski (IN-02), Tony C?rdenas (CA-29), Gus Bilirakis (FL-12), Terri Sewell
(AL-07), and Fred Upton (MI-06).

Currently, Medicare does not automatically cover the latest advances in medical technology, even when the products are approved
or cleared by the FDA and designated a breakthrough product. FDA-approved products can take up to three years to go through the
Medicare coverage determination process, delaying vital treatments to millions of seniors.

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.

-10-
The Ensuring Patient Access to Critical Breakthrough Products Act would require Medicare to temporarily cover all breakthrough
products approved through the FDA for four years. During this period, the Centers for Medicare and Medicaid Services (CMS) would
be required to make a permanent coverage determination. This allows patients and their providers access to the most cutting-edge,
innovative care as soon as it comes to market.

For a medical product to earn the FDA's 'breakthrough" designation, it must meet the following criteria:

¢ Provides more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions;
¢ Has no approved alternatives;

¢ Offers significant advantages over existing approved alternatives; or

¢ Its availability is in the best interest of patients.

The bill also provides temporary coverage for certain breakthrough devices that did not exist or were not considered when Medicare
was first created, like digital therapeutics.

In January, CMS finalized the Medicare Coverage for Innovative Technology (MCIT) rule, which like 2021 CONG US HR 4043 would
provide temporary Medicare coverage for products that have received breakthrough designation by the FDA and help Medicare
beneficiaries access these new technologies. However, the CMS has since delayed implementing this rule.

FDA Participates in New "Collaborative Communities' to Address Emerging Challenges in Medical Devices

On August 4, 2021, the FDA announced participation in several new collaborative communities [FN32] aimed at addressing challenges in

patient health care. Collaborative communities are a continuing forum where private and public sector representatives of the community
work together on medical device challenges to achieve common objectives and outcomes. [FN33]

'We're pleased to announce the progress we've made with participation in collaborative communities. These collaborations with diverse
stakeholders are not only a strategic priority for the FDA's Center for Devices and Radiological Health, they also provide much needed
forums for deep discussion and solution-driven initiatives to tackle important issues within the medical device ecosystem," said Jeff
Shuren, M.D., J.D., director of the FDA's Center for Devices and Radiological Health. 'The insights and outcomes developed by these
groups will have long-standing impacts on public health."

The FDA currently participates in 12 collaborative communities, which are established, managed and controlled by external
stakeholders. Collectively these communities are charting paths to accelerate and address regulatory science and other knowledge
gaps to aid in medical device review and oversight. They may also impact the delivery of healthcare and change clinical care
paradigms.

The most recent collaborations focus on topics such as: medical device development and product quality; understanding of valvular
heart disease; innovations in digital pathology; reducing rates of intended self-injury and suicidal acts by people with diabetes; and
strategies to increase the awareness, understanding and participation of racial and ethnic minorities in the medical technology industry.
The FDA participates in these collaborative communities:

* Collaborative Community on Ophthalmic Imaging

* National Evaluation System for health Technology Coordinating Center (NESTcc) Collaborative Community
¢ Standardizing Laboratory Practices in Pharmacogenomics Initiative (STRIPE) Collaborative Community

¢ International Liquid Biopsy Standardization Alliance (ILSA)

¢ Xavier Artificial Intelligence (Al) World Consortium

« Case for Quality Collaborative Community

¢ Heart Valve Collaboratory (HVC)

¢ Wound Care Collaborative Community

¢ Pathology Innovation Collaborative Community (PICC)

* REducing SuiCide Rates Amongst IndividUals with DiabEtes (RESCUE) Collaborative Community

¢ MedTech Color Collaborative Community on Diversity and Inclusion in Medical Device Product Development and Clinical Research
(MedTech Color Collaborative Community)

¢ Digital Health Measurement Collaborative Community (DATAcc)

'The number of collaborative communities has continued to grow, showing that, amidst the backdrop of the COVID-19 pandemic, many
remain dedicated to the idea that together, they can better achieve common outcomes, solve shared challenges and leverage collective
opportunities to improve public health," said Michelle Tarver, M.D., Ph.D., deputy director of the Office of Strategic Partnerships and
Technology Innovation in the FDA's Center for Devices and Radiological Health.

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.

-11-
FDA Issues De Novo Classification Rule

On October 5, 2021, the FDA issued a final rule [FN34] +9 establish requirements for the medical device De Novo classification process
under the Federal Food, Drug, and Cosmetic Act (FD&C Act). This final rule establishes procedures and criteria related to requests for
De Novo classification ('De Novo request") and provides a pathway for certain new types of devices to obtain marketing authorization
as class | or class II devices, rather than remaining automatically designated as a class III device, which would require premarket
approval under the post amendments device classification section of the FD&C Act.

The De Novo classification process is intended to provide an efficient pathway to ensure the most appropriate classification of a
device consistent with the protection of the public health and the statutory scheme for device regulation. When FDA classifies a
device type as class | or II via the De Novo classification process, other manufacturers do not necessarily have to submit a De Novo
request or premarket approval application (PMA) to legally market a device of the same type. Instead, manufacturers can use the less
burdensome pathway of premarket notification (510(k)), when applicable, to legally market their device, because the device that was
the subject of the original De Novo request can serve as a predicate device for a substantial equivalence determination.

The rule provides that:
- A person may submit a De Novo request after submitting a 510(k) and receiving a not substantially equivalent (NSE) determination.

- A person may also submit a De Novo request without first submitting a 510(k), if the person determines that there is no legally
marketed device upon which to base a determination of substantial equivalence (SE).

- FDA will classify devices according to the classification criteria in the FD&C Act. FDA classifies devices into class | (general controls)
if there is information showing that the general controls of the FD&C Act are sufficient to reasonably assure safety and effectiveness;
into class II (special controls) if general controls, by themselves, are insufficient to provide reasonable assurance of safety and
effectiveness, but there is sufficient information to establish special controls to provide such assurance; and into class III (premarket
approval) if there is insufficient information to support classifying a device into class | or class || and the device is a life-sustaining or life-
supporting device or is for a use which is of substantial importance in preventing impairment of human health or presents a potential
unreasonable risk of illness or injury.

- Devices will be classified by FDA by written order.

- A De Novo request includes administrative information, regulatory history, device description, classification summary information,
benefits and risks of device use, and performance data to demonstrate reasonable assurance of safety and effectiveness.

- FDA may refuse to accept a De Novo request that is ineligible or that is not sufficiently complete to permit a substantive review.

- After a De Novo request is accepted, FDA will begin a substantive review of the De Novo request that may result in either FDA
requesting additional information, issuing an order granting the request, or declining the De Novo request.

- FDA may decline a De Novo request if, among other things, the device is ineligible or insufficient information is provided to support De
Novo classification.

¢ The rule also describes the practices for the conditions under which the confidentiality of a De Novo file is maintained.

© Copyright Thomson/West - NETSCAN's Health Policy Tracking Service

 

[FN2]
. 2020 WLNR 36008848

[FN3]
. 2020 WLNR 36281244

[FN4]
. Available at: https://Awww.fda.gov/media/145022/download

[FN5]
. 2021 WLNR 1173733

[FN6]
. 2021 WLNR 3994179

[FN7]
. 2021 WLNR 5412448

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.

-12-
[FN8]
. 2021 WLNR 6576746

[FN9]
. 2021 WLNR 6880128

[FN10]
. 2021 WLNR 8957191

[FN11]
. 2021 WLNR 10053496

[FN12]
. 2021 WLNR 10053387

[FN13]
. 2021 WLNR 11645580

[FN14]
. 2021 WLNR 13306681

[FN15]
. 2021 WLNR 17902229

[FN16]
. 2021 WLNR 28172923

[FN17]
. 2021 WLNR 31139897

[FN 18]
. 2021 WLNR 32252899

[FN19]
. 86 FR 58150

[FN20]
. 2021 WLNR 34339486

[FN21]
. 86 FR 36987

[FN22]
. 2021 WLNR 35333965

[FN23]
. 2021 WLNR 37633705

[FN24]
. 2021 WLNR 5699856

[FN25]

. Available at: https://www.nejm.org/doi/10.1056/NEJMc2029240?url_ver=Z39.88-2003&rfr_id=ori#rid#crossref.org&rfr_dat=cr_pub+

+0Opubmed+#*l+article_citing_articles

[FN26]
. 2021 WLNR 15630615

-13-

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.
[FN27]

. Available at: https://www.fda.gov/medical-devices/letters-health-care-providers/stop-new-implants-medtronic-hvad-system-letter-
health-care-providers

[FN28]
. 2021 WLNR 17119472

[FN29]

. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarket-surveillance-under-section-522-
federal-food-drug-and-cosmetic-act-0

[FN30]

. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/procedures-handling-post-approval-studies-
imposed-premarket-approval-application-order

[FN31]

. Available at: https://delbene.house.gov/uploadedfiles/breakthrough_products_marked_for_intro.pdf

[FN32]

. Available at: https://www.fda.gov/about-fda/cdrh-strategic-priorities-and-updates/collaborative-communities-addressing-health-care-
challenges-together

[FN33]
. 2021 WLNR 25338365

[FN34]
. 86 FR 54826-01

Produced by Thomson Reuters Accelus Regulatory Intelligence 24-Jan-2022

THOMSON REUTERS

 

© 2022 Thomson Reuters. No claim to original U.S. Government Works.

-14-