Showing all posts written by Alexander Zeng
Prior to joining the firm, he worked as a research scientist for Dr. Hussein Yasine at USC where he was involved with research on the effect of APOE e4 on brain lipids. He graduated from the University of California Los Angeles with his B.S. in Bioengineering and the University of Southern California with his M.S. in Medical Device and Diagnostic Engineering.
During law school at the University of California Irvine, Alexander was a Research Editor on Law Review and was a member of the UCI Intellectual Property, Art, and Technology clinic where he worked on start-up counseling, trademark prosecution, and fair use analysis for documentary film makers.
On December 1, 2021, RefleXion Medical, Inc. (“RefleXion”), announced that the U.S. Food and Drug Administration (“FDA”) has granted the company breakthrough device designation for its biology-guided radiotherapy (“BgRT”) for lung tumors.
is a voluntary program for certain medical devices and device-led combination products that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions. The goal of the Breakthrough Devices Program is to provide patients and health care providers with timely access to these medical devices by speeding up their development, assessment, and review, while preserving the statutory standards for premarket approval, 510(k) clearance, and De Novo marketing authorization, consistent with the Agency’s mission to protect and promote public health.
According to RefleXion, “the breakthrough potential of BgRT lies in its ability to detect and then immediately treat moving tumors. It is the first and only technology to use injected radiotracers to produce active signals, called emissions, from each tumor to guide treatment delivery” and “aims to remove the uncertainty of guiding radiation delivery using images taken days before treatment.” Many patients with stage four cancer cannot use current forms of radiotherapy because existing technology is unable to efficiently track and treat multiple tumors. “The unmet need in lung cancer is staggering,” said Todd Powell, president and CEO of RefleXion. According to Cancer.Org, “[l]ung cancer is the most common cause of cancer-related death,” accounting for 25% of all cancer deaths in the United States.
As RefleXion explains, the use of PET emissions in BgRT to guide treatment makes the “cancer itself act as a fast, biological fiducial continuously signaling its locations even during motion.” As the PET tracer collects in the tumor, “a series of positron annihilation events occur resulting in the emission of two photons almost 180 degrees to each other.” The detector in the RefleXion X1 device finds these emissions and outputs images in real time. A video of RefleXion’s X1 Machine (shown below), used for BgRT, can be seen here.
According to an article published in Nature Biotechnology, Harvard and MIT researchers invented a face mask for detecting SARS-CoV-2, the virus that causes COVID-19, via a user’s breath. Instead of relying on a lab, the personal device uses sensors that use wearable freeze-dried cell-free (wFDCF) technology. This technology contains the same molecules that cells use to recognize and manipulate nucleic acids and proteins. According to MedGadget, unlike previous iterations of this technology which store living cells in “tiny aquariums”, wFDCF technology prevents any issues with leakage due to breakage.
To use the mask, a user presses a button on the mask to release water onto reactive wFDCF sensors. MedGadget reports that results are given within 90 minutes and can be displayed on the inside of the mask for privacy purposes. According to the scientific article, the wFDCF technology first cleaves viral particle samples in order to release the viral RNA. Next, target genes located in the viral RNA are amplified via reverse transcription–recombinase polymerase amplification, in order to amplify the sequence that encodes for the spike protein. A lateral flow assay strip is then used to display visual results similar to a pregnancy test.
“We have essentially shrunk an entire diagnostic laboratory down into a small, synthetic biology-based sensor that works with any face mask, and combines the high accuracy of PCR tests with the speed and low cost of antigen tests,” said researcher Peter Nguyen. “In addition to face masks, our programmable biosensors can be integrated into other garments [e.g., lab coats] to provide on-the-go detection of dangerous substances including viruses, bacteria, toxins, and chemical agents.”
MIT News reports that the device can also swap in sensors for other pathogens, including influenza, Ebola, and Zika, or sensors they have developed to detect organophosphate nerve agents.
Genetic Engineering and Biotechnology News reports that the research team is “actively searching for manufacturing partners who are interested in helping to enable the mass production of the face mask diagnostic for use during the COVID-19 pandemic, as well as for detecting other biological and environmental hazards.” The article reports that the authors have already submitted provisional patent applications for the technology.
The original article was published in Nature Biotechnology on June 28, 2021, and is available here.
COVID-19-related web applications have been popping up from the very start of the pandemic, and many, including Apple and others, have stepped up to contribute to the developments. The majority of COVID-related applications attempt to tackle the effort of contact tracing in order to get a better grasp on where the virus is spreading. Many of them have taken on a variety of approaches to tackle the issue – some apps are optional while others have mandated downloads. The MIT Technology Review Covid Tracing Tracker goes into an in-depth evaluation of the 25 applications it was able to identify. For example, Turkey requires all residents who have tested positive for COVID-19 to download Hayat Eve Sığar and share their data with the police, while India has become the only democracy that is making its app Aarogya Setu mandatory for millions of its people. On the other end of the spectrum are apps like Austria’s Stopp Corona and Iceland’s Rakning C-19, which are entirely voluntary to use.
Like many other players in the market, Apple also plans to build out a contact-tracing application in partnership with Google. However in the meantime, Apple released a US-focused website and app simply titled COVID-19 at the end of March. The goal of the website and app is to “help people stay informed and take the proper steps to protect their health during the spread of COVID-19.” To achieve this, the website notes that Apple provides users with a Screening Tool to help assess their condition and risks, and supplements that with a variety of COVID-19-related information. Contact tracing is not part of the app and website’s functions.
According to the press release, the Screening Tool can be used to evaluate your own condition or complete the screening on someone else’s behalf. Before diving into the questionnaire, users are shown a list of symptoms that would constitute an emergency and are asked to contact 911 if any of them are present. Once emergencies are ruled out, a list of comprehensive questions asks users the usual symptom and travel-related questions, but also goes into more detail with questions such as “do you work in a medical facility?” and “do you live in a long-term care facility?” At the end of the questionnaire, users are presented with recommendations on next steps, which for some may include testing for COVID-19, or reaching out to a healthcare professional. When using the app, the questionnaire answers and recommendations are stored in the app and can be accessed at a later date. When using the website, users will instead see an option to print their results for their records. In either scenario, Apple states that it does not collect answers from your screening, and only collects website/app usage information to improve usability.
The website and application were developed by Apple in partnership with the CDC, The White House, FEMA and local state governments in “a direct response to President Trump’s call for an all-of-America approach and will help Americans heed CDC guidelines and self-isolate to limit COVID-19 transmission.
In July 2018, Citroën, the French car manufacturer, unveiled glasses that aid in alleviating motion sickness. The “Seetoën” glasses, developed by Boarding Ring, purports to eliminate motion sickness symptoms within about 10 minutes of putting them on. According to Boarding Ring, the Boarding Ring technology includes four rings filled with blue liquid.
With the increase of use of smartphones and tablets, motion sickness has been affecting more people as more people look at screens while being transported around. Motion sickness affects up to 66% of the passengers depending on the vehicle. Motion sickness is thought to be caused by a mismatch between the visual information and the balance system’s perceptions. This situation can trigger motion sickness symptoms.
Currently, common remedies for motion sickness include focusing your eyes on the horizon, choosing your seat wisely to minimize motion (e.g., front or driver’s seat in a car, center of a boat, over the wings on a plane), avoiding alcohol and fatty foods, and taking medications such as Dramamine. But these remedies are not necessarily a complete fix. According to the Smithsonian, “some examples include a pair of blinders to block out visual information, a head mounted projection device meant to make visual information line up with sensory information, and shutter glasses that open and close rapidly, meant to prevent the visual slippage associated with motion sickness.”
As explained by Autoevolution, the lens-less glasses “create an artificial horizon line in the front and sides, which allows the resynchronization of sight and inner-ear, and thus ‘cures’ motion sickness. Put them on and look at a fixed object, such as tablet or phone or book, and you should be able to remove them after 10 minutes[.] [Afterwards,] your motion sickness symptoms [will be] all gone.” The glasses use a concept that is similar as looking at the horizon when experiencing motion sickness at sea. The horizon provides a stable reference point for our brains to focus on, thus alleviating the confusion that other senses create when sending confusing information to our brains. Alleviating motion sickness can be performed by putting on the Seetoën glasses as soon as symptoms start to occur. The Seetroëns can be worn over prescription lenses. Once symptoms disappear, one can simply remove the glasses and enjoy the rest of their trip.
However, there are critics who remain skeptical of the effectiveness of the glasses. Thomas Stoffregan, a professor of kinesiology at the University of Minnesota states that “[p]eople have been trying to use an artificial horizon in the context of motion sickness for several decades, at least since the 1970s …It’s never worked. My question to this company is ‘what’s different about your virtual horizon?’” In response, Boarding Ring’s CEO Antoine Jeannin says the Boarding Glasses are unique because they bring an artificial horizon to the peripheral vision—that’s why the glasses have four lenses—unlike other products, which only engage the central vision.
The glasses were invented by the father of Antoine Jeannin, Hubert Jeannin. According to the Smithsonian, “Hubert Jeannin patented his innovation in 2004 (the ’237 Patent) and tested the Boarding Glasses prototypes with the French navy, and, although the exact results are confidential, his son says it was extremely successful—some 95 percent of users found the glasses helpful within 10 minutes.
A new study based on a novel implantable weight loss device that was published in Nature, has shown that it was able to help rats shed almost 40 percent of their body weight. This implant device developed by engineers at the University of Wisconsin–Madison could offer a promising new weapon for the battle against obesity. More than 700 million adults and children worldwide are obese, according to a 2017 study that called the growing number and weight-related health problems a “rising pandemic.”
According to articles, the device itself is minuscule – measuring less than 1 centimeter across. The devices are said to be safe for use in the body and implantable via a minimally invasive procedure and is powered by the stomach’s natural churning motion. The devices are also said to generate a gentle electric pulse to the vagus nerve, which links the brain and the stomach, and signals to the brain that the stomach is full even after a small snack.
According to the University of Wisconsin –Madison, “[u]nlike gastric bypass surgery, which permanently alters the capacity of the stomach, the effects of the new devices are reversible. When Wang and his collaborators removed the devices after 12 weeks, the study’s rats resumed their normal eating patterns and weight bounced right back on.”
Articles have stated that the new device also has several advantages over existing devices that stimulates the vagus nerve for weight loss. That existing unit, “Maestro,” approved by the Food and Drug Administration in 2015, administers high-frequency pulses to the vagus nerve to block all communication between the brain and stomach. The Maestro device also require batteries which frequently must be recharged. In contrast, “Wang’s device contains no batteries, no electronics, and no complicated wiring. It relies instead on the undulations of the stomach walls to power its internal generators. That means the device only stimulates the vagus nerve when the stomach moves.”
On May 30, 2018, the U.S. Food and Drug Administration launched an innovation challenge as a way to combat the fight against opioid addiction. The challenge was issued to “spur the development of medical devices, including digital health technologies and diagnostic tests that could provide novel solutions to detecting, treating and preventing addiction, addressing diversion and treating pain.”
FDA Commissioner Scott Gottlieb stated that “[m]edical devices, including digital health devices like mobile medical apps, have the potential to play a unique and important role in tackling the opioid crisis.” Medical devices can be used to address opioid addiction by, for example, effectively addressing local pain syndromes in order to supplant the use of systemic opioids and reduce the use of opioids. “New digital technology products and diagnostic tests could help in the opioid addiction fight by detecting, treating, and preventing addiction; addressing diversion of the opioid supply chain to illicit use; and treating pain,” the FDA said.
According to Bloomberg, “accepted companies will get to work more closely with the FDA’s review offices than usual to help get their products approved. Products that qualify as breakthrough devices under food and drug law will receive that designation without the sponsor needing to submit an application, the agency said. A breakthrough device designation can reduce the time and cost to get a product to market that addresses life-threatening or irreversibly debilitating diseases.”
The innovation challenge is open to any product in any stage of development. The challenge also is open to developers of currently marketed devices who can show that their devices have an improved benefit-risk profile compared to opioid use in pain management. The FDA anticipates “that applicants will eventually submit one or more formal applications to the FDA, such as an investigational device exemption, De Novo, premarket clearance (510(k)) or premarket approval application.”
This innovation challenge is part of the FDA’s plan to aid in the opioid crisis and supports several overarching goals of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis. On April 20, 2018, the agency also released the first of two new draft guidances intended to aid industry in developing new medications for use in medication-assisted treatment (MAT) for opioid dependence.
According to Bloomberg, Apple, Inc. is currently developing an electrocardiogram (also known as an EKG or ECG) feature in its smartwatch products. A report from Bloomberg and other sources have stated that the unit in development requires users to squeeze the frame with two fingers to send a weak electrical current to the heart to pick up signals. The electrical current is used to track a user’s electrical heart signals in order to determine if there are any abnormalities such as irregular heart beats. The Verge states that “[s]ensors and data gathered from minor electric currents sent up the arm and across the chest to the user’s heart would measure data typically gathered by electrodes on the skin.” This would let users obtain a constant stream of EKG data that could then better inform doctors with diagnosis and treatment at an early stage. The CDC indicates that abnormal heart beats can increase the risk of strokes and heart failures in individuals.
The article notes that Apple’s current Watch has a basic heart rate monitor, but the company has increasingly trying to use advanced sensors to “predict future afflictions, rather than simply collect historical data about the body. An EKG would make it easier to establish the health of a user’s heart, and potentially spot some cardiac problems early.”
The article further notes that this development is not surprising as Apple has already given up marketing its smartwatch as a luxury watch. When it was first released in 2015, the Apple Watch was largely marketed as a high-end fashion piece. As the “second and third generations went on sale, the focus shifted to health and fitness, with Apple adding alerts for abnormal heart rate spikes.” Apple has now been focusing on using the Watch as a medical device. According to Jeff Williams, Apple’s chief operating officer, “[t]here’s tremendous potential to do on-device computing, to do cloud computing as well and to take that learning, and through machine learning, deep learning and ultimately artificial intelligence, to change the way health care is delivered . . . [w]e can’t think of anything more significant than this.”
Apple has already launched a new study in partnership with Stanford University that will track Apple Watch users’ heart rhythms for irregularity. The Federal Drug Administration also has cleared the Apple Watch’s first medical device accessory, an EKG reader built into a watch strap from medical device company AliveCor.
According to Bloomberg, the “health industry’s size has made it attractive for tech giants seeking new growth markets. U.S. health spending is forecast to grow from almost $3.5 trillion in 2016 to $5.5 trillion by 2025” according to data compiled by Bloomberg. Other corporate giants such as Google parent Alphabet Inc. already have two health-care divisions, while Amazon.com Inc. has for almost two decades been looking at ways to get into the pharmaceutical industry.
One of the largest hurdles for these companies to enter the medical-device market has been the the strict testing requirements imposed by the U.S.
The FDA may begin certifying the laboratories that produce lab-developed tests (“LDTs”) instead of drafting regulatory rules to cover the tests themselves. The American Clinical Laboratory Association describes LDTs as:
[T]ests that hospitals, academic, and clinical laboratories develop as testing services according to their own procedures. These tests are often created in response to unmet clinical needs, and are commonly used for early and precise diagnosis, monitoring, and guiding patient treatment.
The organization believes that the ability to innovate and design custom diagnostic tests has been critical to the growth of personalized medicine and keeping pace with the changes in the medical profession.
According to Sean Khozin, associate acting director of the FDA’s Oncology Center of Excellence, the program will be modeled after the FDA’s pilot approval process for digital health products. This process functions as a stamp of approval by the FDA, Mr. Khozin explained that:
The precertification program represents a modern approach to regulation, shifting the focus from the product, to the developer of the product . . . . That product then doesn’t necessarily have to go through analytical validation process.
This program may be compared to to the Digital Health Software Precertification (“Pre-cert”) Program that was announced in July, 2017. The agency picked nine companies for the program, including Alphabet Inc. (Google’s parent company), Apple Inc., and Fitbit Inc. Under the Digital Health SOftware Pre-cert program, the FDA will examine the software (rather than the device itself) and inspect facilities to ensure they meets the FDA’s standards. If the companies pass the audit, the companies will attain pre-certified status and their products will be pre-cleared in lieu of being examined by the FDA’s traditional regulatory framework.
Regulating LDTs has been an issue that the FDA has considered in response to a “boom” in the diagnostics industry and as more physicians demand complex tests to screen for diseases like breast cancer and Alzheimer’s.
The medical device and clinical laboratory industries have been at odds over the question of LDT regulation since 2014, when the FDA first sought to regulate LDTs. Device makers supported the FDA’s regulation-based approach while clinical labs, which were already regulated by the Clinical Laboratory Improvement Amendments (CLIA) under the Centers for Medicare & Medicaid Services, disagreed. The FDA dropped its enforcement proposals in 2016. The American Clinical Laboratory Association, whose members traditionally have been regulated under CLIA, said:
[The ACLA] has consistently maintained that LDTs are not medical devices and cannot be regulated as such. The decision by the FDA last year to not issue final guidance to regulate LDTs was a victory for diagnostic innovation and for patients.
The FDA is now expected to announce a new pilot plan soon to certify laboratories that develop diagnostic tests in lieu of drafting rules for the tests themselves. The plan for the LDTs do not seem to conflict with CLIA rules as the CLIA rules does not concern manufacturers, the CLIA rules concern labs.
The FDA recently approved Abott’s FreeStyle Libre Flash Glucose Monitoring System. According to Bloomberg, this device marks the first continuous glucose monitoring system that adults can use that does not use diagnosis via taking fingertip blood samples using a fingerstick.
Traditionally, fingersticks required one to prick their finger to obtain blood droplets for diabetes monitoring devices to work. The Libre flash instead uses a more discreet method of operation–a small sensor wire is inserted below the skin’s surface which continuously measures and monitors glucose levels. According to Abbott, a mobile reader is used to measure glucose levels when a user waves the mobile reader above the sensor wire. It is intended for use in people 18 years of age and older with type I or II diabetes. After an initial 12-hour acclimation period, it can be worn for up to 14 days. Because a diabetic patient’s pancreas can not produce insulin, those patients frequently must monitor their blood sugar and regularly inject themselves with insulin when their blood sugars spike.
Bloomberg and Reuters report that other companies have been left behind. Johnson & Johnson is closing its insulin-pump unit after failing to keep up with Medtronic Plc. DexCom Inc., the current leader in glucose-monitoring systems, which, in turn, lost a third of its market value on Sept. 28 after Abbott’s Libre got approval.
The Centers for Disease Control and Prevention notes that more than 30 million people in the U.S. have diabetes. People with diabetes either do not make enough insulin (type 1 diabetes) or cannot use insulin properly (type 2 diabetes). When the body doesn’t have enough insulin or cannot use it effectively, sugar builds up in the blood. High blood sugar levels can lead to heart disease; stroke; blindness; kidney failure; and amputation of toes, feet or legs.
According to Bloomberg, “the bulk of the sales are to the 1.25 million American diabetes patients with the most severe form of the disease, type 1. There’s a larger, mostly untapped market: the about 20 million Americans with type 2, whose body’s ability to use insulin fades slowly over time and who don’t regularly use tools to manage their disease.”
On September 26, 2017, the FDA announced that it has chosen nine tech companies to participate in a pilot program (FDA Pre-Cert) to help tech companies bypass some regulations that have hindered health software and products release, Bloomberg reports. According to the Bloomberg article, this program operates as a “fast track” for these technology companies, which amongst others include Apple, Fitbit, Samsung, Johnson & Johnson, and Verily Life Science (an arm of Google parent Alphabet Inc.), and is said to allow them to develop technologies rapidly, while allowing the FDA to maintain oversight over those projects.
This program is said to signal a broader trend at the FDA to streamline regulation since FDA Commissioner Dr. Scott Gottlieb was appointed in May. Bloomberg reports that as technology companies have entered the healthcare and medical device arena, questions arose of whether these companies were required to seek FDA approval on their products. For example, in 2013, the consumer gene-testing company 23andMe Inc. was ordered by the agency to temporarily stop selling its health analysis product until it was cleared by regulators. “We need to modernize our regulatory framework so that it matches the kind of innovation we’re being asked to evaluate,” Commissioner Gottlieb said.
As Fortune reports, the pilot companies can potentially get their products pre-cleared in lieu of undergoing the FDA’s traditional medical device regulatory framework. Under FDA Pre-Cert, the FDA will instead primarily examine the software (rather than the tech device itself) and inspect facilities to ensure it meets the FDA’s rigid standards. If the companies pass the audit, the companies will attain pre-certified status. The FDA Pre-Cert was launched as part of the agency’s Digital Health Innovation Action Plan. The press announcement states that the “plan seeks to outline the agency’s vision for fostering digital health innovation while continuing to protect and promote public health by providing clarity on medical software provisions of federal legislation passed in 2016 (21st Century Cures), adding expertise to the digital health unit and initiating the FDA Pre-cert pilot program.” The FDA plans to share public updates via the pilot program webpage as well as through stakeholder meetings, including a January 2018 workshop.
For more information on the FDA’s Pre-Cert press release, please visit the site here.