Brain Computer Interface Developer Announces $33M Series A, Granted FDA “Breakthrough” Designation
Brain computer interface developer Paradromics on May 18, 2023, announced a $33 million Series A funding round as well as a “Breakthrough Device Designation” from the FDA.
The funding is reportedly for the company’s first-in-human clinical trial of the brain computer interface technology, named the Connexus® Direct Data Interface (DDI). The company states that “[t]he first application of the Connexus DDI is an assistive communication device that translates brain signals into speech and movement in real time, restoring social connection and enabling independent engagement with technology.”
The company reports that the funding round is being led by Prime Movers Lab, with the other investors including Westcott Investment Group, Dolby Family Ventures, and Green Sands Equity.
The FDA describes the Breakthrough Device Designation program as 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 program is intended “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.”
The company’s press release is available here, and more information on the Breakthrough Device Designation program from the FDA is available here.
AI & the FDA
The use of artificial intelligence (AI) in healthcare has been growing rapidly in recent years, and AI-enabled medical devices are playing a larger role in patient care. Such devices may use machine learning algorithms to analyze vast amounts of patient data and provide diagnoses as well as personalized treatment recommendations. In recent years, the FDA has approved various AI-enabled medical devices, some of which are discussed below.
IDx-DR is an AI-powered diagnostic system for detecting diabetic retinopathy (a complication of diabetes that can lead to blindness) through the analysis of retinal images. The system reportedly uses machine learning algorithms to analyze images and make a diagnosis, without the need for a specialist to interpret results. IDx-DR was the first FDA-approved autonomous AI diagnostic system for use in any field of medicine.
Viz.ai LVO Stroke Platform is an AI-powered platform for analyzing CT scans of the brain to identify large vessel occlusions that can indicate a potential stroke. The system reportedly uses machine learning algorithms to analyze CT scan images and alert healthcare providers when a potential stroke is detected and that rapid treatment may be required, allowing for improved patient outcomes. Viz.ai LVO is the first FDA-approved AI platform for stroke detection and triage.
ProFound AI for Digital Breast Tomosynthesis (DBT) is an AI-based software from iCAD, Inc. for analyzing tomosynthesis images to assist radiologists in detecting breast cancer. The system reportedly uses machine learning algorithms to analyze mammograms and identify potential areas of concern (e.g., malignant soft tissue densities and calcifications), providing radiologists with a second opinion and improving diagnostic accuracy. ProFound AI was the first 3D tomosynthesis software using artificial intelligence (AI) to be cleared by the FDA, and the software’s current third generation has also received FDA clearance.
Eko DUO is an AI-enabled stethoscope for analyzing heart sounds and detecting potential cardiac abnormalities. The Eko DUO stethoscope, when used with the Eko App, reportedly uses machine learning algorithms to identify specific heart sounds and detect cardiac abnormalities including atrial fibrillation (AFib), murmurs, tachycardia, and bradycardia. Eko DUO is the first FDA-approved AI-enabled stethoscope for use in a clinical setting.
Caption Guidance is an AI-based software from Caption Health that assists in the acquisition of cardiac ultrasound (echocardiogram) images. The software reportedly uses AI to assess the diagnostic quality of such images in real-time, which helps guide healthcare providers in capturing echocardiogram images that are of sufficient diagnostic quality. The FDA authorized the marketing of Caption Guidance in February 2020, making Caption Guidance the first FDA-authorized software for guiding users through cardiac ultrasound image acquisition.
FDA Issues Final Guidance on Transitioning from COVID-19 EUAs
The FDA recently announced release of final transition guidance documents for medical diagnostic devices targeting COVID-19. The transition guidance documents are intended to guide COVID-19 diagnostic device manufactures as their devices transition from Emergency Use Authorizations (EUAs). Just over three hundred EUAs were issued for diagnostic devices during the COVID-19 pandemic. In the announcement, the FDA characterized the issuance of EUAs as “proactive steps to help facilitate the availability of critical medical devices, including in vitro diagnostic tests.” Draft versions of the guidance documents were made available for public comment in December 2021.
The FDA’s announcement follows the recent White House announcement that the COVID-19 Public Health Emergency is set to expire on May 11, 2023. Though the initial public health emergency announcement authorized use of EUAs for various COVID-related products, the end of the public health emergency does not automatically terminate the pending EUAs. Instead, the Department of Health & Human Services (HHS) will publish notice of termination of each EUA declaration 180 days in advance. Notice will publish in the Federal Register.
The final transition guidance documents clarify recommendations for labeling, post-EUA disposal of diagnostic devices, and use of real-world evidence in FDA marketing submissions. Additionally, the transition guidance documents clarify the relationship between the transition period guidance and the previous COVID-19 guidance from the FDA (i.e., those found in List 1 of the Transition Plan, including guidance on digital pathology, imaging systems, non-invasive fetal and maternal monitoring, and other technologies).
Industry groups, for example AdvaMed and MITA, had previously expressed approval via public comment of the 180-day transition period proposed by the draft guidelines.
The FDA has encouraged device manufacturers that plan to seek marketing authorization to begin working on a marketing submission soon.
The FDA will be holding a webinar to answer questions about the transition on April 18, 2023.
Patent on Controlling Access to Drug Delisted from Orange Book
On February 24, 2023, in Jazz Pharms., Inc., v. Avadel CNS Pharms., LLC, the U.S. Court of Appeals for the Federal Circuit affirmed the United States District Court for the District of Delaware’s grant of an injunction directing Jazz Pharmaceuticals, Inc. (“Jazz”) to delist U.S. Patent 8,731,963 (“the ’963 patent”) from the Orange Book.
The ’963 patent is directed to Jazz’s single-pharmacy distribution system, which controls access to abuse-prone drugs prescribed to narcolepsy patients, such as Jazz’s narcolepsy drug—XYREM®. In 2014, Jazz listed the ’963 patent in the Orange Book as covering a method of using sodium gamma hydroxybutyrate (GHB), the active ingredient of XYREM®. After Avadel CNS Pharmaceuticals, Inc. (“Avadel”) submitted a New Drug Application (NDA) for GHB-based drug FT218, Jazz sued Avadel for infringement. Avadel counterclaimed seeking to delist the ’963 patent for failing to claim a drug or method of use.
Under 21 U.S.C. § 355(b), a patent may be listed in the Orange Book if the patent claims an approved drug or “claims a method of using such drug for which approval is sought or has been granted in the application.” Here, the Federal Circuit held that the ’963 patent is not a properly listable method-of-use patent, as the claims are directed to a “computer-implemented system.” Accordingly, the Federal Circuit affirmed the district court’s decision to delist the ’963 patent from the Orange Book.
Since 2020, combination products, such as pre-filled syringes, inhalers, and transdermal patches, have become more prevalent. Similar trends are anticipated for drug-delivery devices, which contain an approved drug and have a device primary mode of action. Section 3038 of the 21st Century Cures Act incorporated several provisions of the Hatch-Waxman Act into the clearance and approval process for drug-delivery devices. However, the Federal Circuit highlighted the differences between method claims, as requiring the performance of steps, and system or apparatus claims, as describing physical components of a whole. Thus, patentees of combination products and drug-delivery devices seeking Orange Book listing should consider both system and methods of use claims.
The Federal Circuit’s decision is available here.
Cochlear Implant Developer Agrees to Pay for Alleged False Claims to FDA
Cochlear implant developer Advanced Bionics LLC will pay about $12 million to resolve allegations that it misled federal health care programs, the United States Department of Justice (DOJ) announced. The allegations were in connection with information provided within pre-market approval (PMA) applications to the FDA for cochlear implant processors, as reported by a DOJ press release dated December 20, 2022.
A former Advanced Bionics engineer, David Nyberg, brought a lawsuit against Advanced Bionics under the False Claims Act. The lawsuit asserted that Advanced Bionics made false claims in their PMA submissions to the Food and Drug Administration (FDA) for Advanced Bionics’ Neptune and Naida cochlear implant processors. Advanced Bionics allegedly made false assertions in the PMA submissions stating that the processors complied with a recognized emissions standard when the processors, in fact, did not comply with the standards.
As a result of the agreement, Advanced Bionics will pay roughly $11.36 million to the United States with approximately $1.87 million of the amount being paid to Mr. Nyber. Advanced Bionics will also pay approximately $1.24 million to the participating Medicaid States pursuant to additional agreements.
BIOCORP Receives FDA 510(k) Clearance for Smart Injection Sensor
French medical device company BIOCORP announced in a press release that it received FDA 510(k) clearance for Mallya, a device that according to the company allows insulin pen injectors to capture and transmit injection data such as dose, date, and time of injection to a mobile app via Bluetooth.
According to the Mallya website, the device allows users to keep track of their doses as well as share dosage information with family members and medical professionals. BIOCORP offers three models of the Mallya, one for each type of disposable insulin pen. The device, shown below on a pen, comes in two pieces that clip on to the insulin pen and can be removed and reused with new pens.
Mallya first launched in France on April 13, 2021. Since then, it has expanded to several countries, including Japan, Nambia, Netherlands, Romania, South Africa, and Taiwan.
On the recent FDA clearance, Eric Dessertenne, CEO of BIOCORP, commented:
This approval is a major achievement for BIOCORP and all of our employees who have been heavily involved in this regulatory process. This approval marks a historic achievement for BIOCORP as it allows the commercial launch of our Mallya device in the United States and illustrates BIOCORP’s ability to meet the highest regulatory requirements.
Other companies have also expressed interest in integrating insulin technology with Mallya. In March, Diabeloop, a company focused on artificial intelligence-driven insulin systems, announced a partnership with BIOCORP to integrate Mallya into Diabeloop’s automated insulin pumps.
The full BIOCORP press release can be found here.
FDA Grants Breakthrough Device Designation for EndoStim’s GERD Treatment
EndoStim announced on October 25th that the FDA granted a breakthrough device designation for the company’s implantable neurostimulation treatment for drug refractory gastroesophageal reflux disease (GERD).
EndoStim states that its EndoStim System is the first-in-class implantable neurostimulation treatment for GERD. While traditional surgery for the treatment of GERD requires wrapping the stomach around the lower esophagus to strengthen a patient’s lower esophageal sphincter muscle (LES), this system attempts to provide long-term reflux suppression by automatically delivering small electrical signals to the LES. EndoStim states the system accomplishes this through use of a neurostimulator and an implantable bipolar lead, and that the lead is placed within the patient through a minimally invasive laparoscopic procedure, and a physician then programs the neurostimulator using a wireless external programmer.
While the EndoStim System is not yet approved for sale in the U.S., multiple long-term studies, such as a University of Vienna study and a German study, on electrical implants aiding GERD using this system have been reported to have found a sustained improvement in GERD outcomes post-procedure. In discussing the announcement, EndoStim’s chief executive officer, Eric Goorno, stated:
We are pleased that the FDA has recognized the therapeutic potential of the EndoStim System as a new treatment in development for drug refractory GERD.… Our goal is to bring this new therapy to patients as quickly as possible. We look forward to working closely with the FDA to expedite the review of the EndoStim System.
The breakthrough device designation program is designed to provide patients and health care providers with timely access to medical devices for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions by speeding up their development, assessment, and review. The FDA recently updated its draft guidance for its breakthrough device designation program to focus on reducing health and healthcare disparities based on race, sec, ethnicity, and access to care.
This year it is reported that the FDA granted 120 breakthrough device designations through August 3, 2022. Since the program’s inception in 2015, the breakthrough device designation program is reported to have seen 54 devices receive marketing authorization.
FDA to Collaborate with Veterans group on Medical Device Innovation
On September 28, 2022 the FDA announced a collaboration with the Veterans Health Administration (VHA), in particular the VA Ventures Innovation Institute. According to the FDA, the intent of the collaboration is to “help accelerate American medical device innovation to further improve and benefit public health. One goal of the collaboration is providing innovators with “straightforward, reproducible, and cost-effective testing methods throughout the product development cycle.”
Jeff Shuren, M.D., J.D., the director of the FDA’s Center for Devices and Radiological Health stated in the FDA’s announcement of the collaboration that:
This strategic alignment between our organizations creates a unique environment to achieve shared objectives for accelerating patient access to safe, innovative and effective medical devices.
The VHA will host staff from the FDA at the VA Ventures Innovation Institute in Seattle. According to the announcement, the FDA staff will be focused on the regulatory science while the VA staff will provide “clinical context for test development and provide hands-on training and other immersive experiences.”
The initial collaboration is described by the FDA as focusing on systems which can “exchange health information automatically for the diagnosis and treatment of patients.” While future areas of collaboration may include “the development of test methods for devices that can be used at a distance through, for example, 5G networks.”
Dr. Shereef Elnahal, the VA’s Under Secretary for Health, stated in the FDA announcement:
By working side by side, VA and FDA will leverage our combined strengths and expertise to bring the most promising health care technology innovation to Veterans – and Americans at large – faster than before.
The announcement by the FDA is available here.
FDA Publishes Draft Ethical Consideration Guidance to Protect Children Participants in Clinical Trials of Medical Products
On September 23, 2022, the Food and Drug Administration (FDA) published a draft guidance aimed to protect children who participate in clinical trials, titled Ethical Considerations for Clinical Investigations of Medical Products Involving Children. The draft guidance describes the FDA’s current position regarding ethical considerations for clinical investigations of drugs, biological products, and medical devices involving children. The guidance explains the fundamental concepts for the ethical framework that institutional review boards (IRBs), sponsors, and the industry should consider when reviewing or conducting clinical trials involving children.
Of note, the guidance outlines additional considerations and recommendations IRBs should assess when enrolling children in clinical investigations of medical products. The guidance explains that, in principal, the risk of the clinical investigations must be balanced by the prospect of direct and potential benefits and must at least be as favorable as any available accepted alternative treatment. Accordingly, the guidance suggests medical product developers need to use a dose or treatment level expected to be effective for the child which should also have a positive impact on the child’s life.
The FDA’s Office of Pediatric Therapeutics noted that “the best way to provide children with safe and effective treatment options is by including them in clinical research.” The Office of Pediatric Therapeutics further noted that children are afforded additional safeguards when participating in a clinical investigation since they are a vulnerable class who cannot provide informed consent for themselves. The FDA’s guideline comes at an important time. By way of example, although 48.2% to 72.6% of parents are willing to vaccinate their children against the COVID-19 virus, a lower rate of parents allow their children to participate in clinical trials.
The FDA’s draft guidance is available here, and is available for comments until December 27, 2022.
FDA Publishes New Monkeypox and Medical Devices Web Page
The FDA has published new web pages about Monkeypox and medical devices. The new web page, titled Monkeypox and Medical Devices, includes information on diagnostic testing, Laboratory Developed Tests (LDTs), and information for test developers. With more than 22,000 confirmed Monkeypox cases in the U.S., the new Monkeypox Medical Devices web comes as FDA takes significant actions to increase Monkeypox testing capacity nationwide following the Secretary of Health and Human Services’ August 9th announcement of public health emergency.
The FDA’s guidance issued for test developers under Policy for Monkeypox Tests to Address the Public Health Emergency describes, among other things, review priorities of Emergency Use Authorization (EUA) requests for monkeypox diagnostic tests. And, on the same day as the FDA guidance was issued, the FDA also issued the first EUA to a commercially available monkeypox test in the United States to Quest Diagnostics for its Quest Diagnostics Monkeypox Virus Qualitative Real-Time PCR device. “With this FDA emergency authorization, Quest is positioned to complement the response of public health laboratories and help fight the spread of the virus,” said Jay G. Wohlgemuth, M.D., Senior Vice President, R&D, Medical and Chief Medical Officer, Quest Diagnostic.
Quest Diagnostics is not the only company that has been working on monkeypox diagnostic test kits. Earlier in June, Becton Dickinson announced partnership with CerTest Biotec to collaborate on molecular diagnostic test for monkeypox. Several other healthcare and pharmaceuticals companies have also been linked with this effort. This comes at a time when many of these companies are preparing for a drop in revenue from COVID-19 testing as the threat of COVID-19 reduces.
USPTO Issues Notice Regarding Patent Examinations and FDA Submissions
On July 29, 2022, the United States Patent and Trademark Office (USPTO) issued a Notice by Director Kathy Vidal that may be relevant to those seeking or holding patents on medical devices that require Food and Drug Administration (FDA) approval. The Notice relates to certain duties owed to the USPTO with regard to statements and documents submitted to the FDA and other government agencies. The duties include a duty to disclose certain information and a duty of reasonable inquiry.
The Notice states “[t]he duty of candor and good faith in dealing with the USPTO includes the duty to disclose to the USPTO information material to the patentability of a claimed invention.” Further, “[e]ach party submitting a paper to the USPTO has an additional duty to perform an inquiry that is reasonable under the circumstances, including reviewing documents to identify information that is material to the patentability of a claimed invention.” The Notice states it “is intended to clarify the duties, including as to materials or statements material to patentability or statements made to the USPTO that are inconsistent with statements submitted to the FDA and other governmental agencies.”
The Notice was issued against the backdrop of an Executive Order by President Biden regarding competition in the economy, specifically in the pharmaceutical industry. Additionally, U.S. Senators sent a letter to the USPTO requesting “that the Office ‘take steps to reduce patent applicants’ making inappropriate conflicting statements in submissions to the [USPTO] and other federal agencies.'” Regarding the letter, the Notice further states:
The letter provided a specific example in which “inconsistent statements submitted to the Food and Drug Administration (FDA) to secure approval of a product—asserting that the product is the same as a prior product that is already on the market— can then be directly contradicted by statements made to the [USPTO] to secure a patent on the product.” The Letter noted that such inconsistent statements “should be cause for rejecting the application and, when made knowingly and with bad intent, potentially other sanctions.”
Against this background, the Notice states it “is part of the USPTO’s efforts to put into effect the Administration’s goals and address the Senators’ concerns.”
The Notice thus discusses which parties have a duty to disclose information to the USPTO in various patent examinations and proceedings, and what material information must be disclosed. For example, the duty to disclose “applies to positions taken by applicants or parties involving the claimed subject matter. For instance, in PTAB proceedings, parties should not take a position about the patentability of challenged claims that is inconsistent with positions taken in submissions to other Government agencies regarding the same subject matter.” An example PTAB proceeding is cited which resulted in “suspending a practitioner for four years for failure to correct the written record after learning of inaccuracies in a declaration the practitioner had filed.” The Notice discusses similar duties in the context of patent examination and prosecution.
In addition to the duty to disclose, the Notice discusses the duty of reasonable inquiry and when these two duties arise in dealings with other government agencies besides the USPTO.
FDA Issues Final Guidance on Software as a Medical Device
The FDA continues to address items on its Digital Health Innovation Action Plan. After recently issuing proposed guidance and a pilot program relevant to Software as a Medical Device (“SaMD”), the FDA issued a final guidance regarding SaMD on December 8, 2017. The guidance adopts a set of quality management principles relevant to “software that utilizes an algorithm (logic, set of rules, or model) that operates on data input (digitized content) to produce an output” such as informing, diagnosing, or treating a patient.
In a press release announcing the final guidance, FDA Commissioner Scott Gottlieb stated:
This final guidance provides globally recognized principles for analyzing and assessing SaMD, based on the overall risk of the product. . . . [W]e’re issuing new details on the common principles we and our international partners will use for evaluating the safety and effectiveness of SaMD.
The principles referred to by Commissioner Gottlieb include the following SaMD Quality Management Principles:
- An organizational structure that provides leadership, accountability, and governance with adequate resources to assure the safety, effectiveness, and performance of SaMD;
- A set of SaMD lifecycle support processes that are scalable for the size of the organization and are applied consistently across all realization and use processes; and
- A set of realization and use processes that are scalable for the type of SaMD and the size of the organization; and that takes into account important elements required for assuring the safety, effectiveness, and performance of SaMD.
Commissioner Gottlieb further opined that this guidance and the IMDRF principles within it “provide [the FDA] with an initial framework when further developing [the FDA’s] own specific regulatory approaches and expectations for regulatory oversight.”
Biolase’s Diolase Receives FDA Clearance
This article states that “Biolase, a medical device manufacturer based in Irvine, California, announced that it had received approval from the United States Food and Drug Administration (FDA) for its 940 nm Diolase 10 laser. In addition, the company announced that the FDA had granted approval for use of the device in additional 80 procedures.”
Fenwal Receives FDA Clearance for Therapeutic Plasma Exchange on Its Amicus Separator
The U.S. Food and Drug Administration has cleared Fenwal to market a therapeutic plasma exchange protocol for the company’s Amicus® separator, Fenwal announced today. The Amicus separator from Fenwal is now one of the most advanced cell separation systems available for therapeutic plasma exchange and mononuclear cell collection, which are used to treat a wide variety of diseases and for clinical research.
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