Boston Scientific Exercises Option to Acquire Transcatheter Annuloplasty Ring Developer Millipede Inc.
Global medical device company Boston Scientific has announced on December 27, 2018, that it exercised its option to acquire remaining shares of privately-held medical device company Millipede, Inc. upon its recent successful completion of a first-in-human clinical study. Boston Scientific previously announced on January 24, 2018, an agreement to make a $90 million investment in Millipede. The current press release states the prior agreement included an option for Boston Scientific to “acquire [Millipede’s] remaining shares for $325M at closing, with a $125M payment becoming available upon achievement of a commercial milestone.”
Millipede has developed a non-invasive solution for repair of the heart’s mitral valve. According to Millipede’s website, Millipede’s IRIS Transcatheter Annuloplasty Ring System reshapes the mitral valve annulus of the heart to treat severe mitral regurgitation (MR). MR is caused by a leaking mitral valve, which causes blood to flow backward from the left ventricle into the left atrium. Over time, MR can lead to or accelerate heart failure and rhythm problems. Millipede’s website describes the IRIS system as providing the gold standard in surgical heart valve repair – a complete annuloplasty ring implant. The implant reshapes and reduces the mitral valve annulus opening, enabling return of leaflet coaptation and reduction of MR.
According to Millipede, the implant is delivered via catheter, for example through a small cut in the patient’s leg. This allows patients to avoid invasive open heart surgery, which is necessary for implantation of conventional annuloplasty rings. Millipede describes the transcatheter ring as repositionable and retrievable.
“We are very satisfied with the early results of our clinical program and are excited to see this technology further leveraged by Boston Scientific to expand the mitral repair solutions for patients around the world.” – Randy Lashinski, CEO, Millipede Inc.
Millipede is based in Santa Rosa, California and was founded in 2012 by majority investor Santé Ventures and Steve Bolling, MD, and has been led by CEO Randy Lashinski since 2014.
Boston Scientific describes itself as a worldwide developer, manufacturer and marketer of medical devices, providing a broad range of high performance solutions that address patient needs and aim to reduce the cost of healthcare.
Millipede is a client of intellectual property and technology law firm Knobbe Martens. With close to 275 lawyers and scientists nationwide, Knobbe Martens dedicates its practice to all aspects of intellectual property law including litigation and is consistently ranked among the top intellectual property firms worldwide.
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.”
NAMSA, which describes itself as “the world’s only Medical Research Organization (MRO) that accelerates medical device development through integrated laboratory testing, clinical research and regulatory consulting services,” has announced the acquisition of Reimbursement Strategies, LLC.
According to Mass Device, “NAMSA is a medical device firm that “offers integrated laboratory testing, clinical research and regulatory consulting services.” According to NAMSA, Reimbursement Strategies is a consultancy “focused on reimbursement, health economics and market access for the international life science industry” which “places a significant concentration on providing clients efficacious and timely development outcomes through the organization’s expertise in reimbursement strategy, health economics, medical policy research and coverage advocacy.”
Christopher Rupp, VP of NAMSA’s global marketing and commercial operations stated that the acquisition of Reimbursement Strategies “will allow clients to proactively address the largest challenges of bringing novel devices to the global marketplace—securing appropriate coverage and payment for new and existing technologies.” Rupp continued to state that “We look forward to delivering device manufacturers faster, more cost-effective commercialization results through our comprehensive, full-service development solution.”
The former President of Reimbursement Strategies, LLC, Edward Black, stated, “We are very pleased to join the NAMSA Team as we work together to provide clients the most critical services required to navigate our industry’s complicated global reimbursement landscape.” Black, who is now NAMSA’s Director of Global Reimbursement Strategy, asserted that, “It is more important than ever for device manufacturers to assess reimbursement challenges early so they may fully integrate this planning into regulatory and clinical research pathways to achieve resource efficiencies and expedite market commercialization.”
According to Business Wire, “NAMSA’s MRO® Approach plays an important role in translational research, applying a unique combination of disciplines—consulting, regulatory, reimbursement, preclinical, toxicology, microbiology, chemistry, clinical and quality—to move clients’ products through the development process, and continue to provide support through commercialization to post-market requirements anywhere in the world.” Business Wire also reports that, “NAMSA operates 13 offices throughout North America, Europe, the Middle East and Asia, and employs nearly 1,000 highly-experienced laboratory, clinical and consulting Associates.”
Garmin and ActiGraph Collaborate to Explore Health and Activity Monitoring Solutions on Wearable Devices
Garmin International, Inc. recently announced a collaboration with ActiGraph to create health and activity monitoring solutions for academic research, clinical trials, and remote patient monitoring. The collaboration will combine Garmin wearables with ActiGraph‘s CentrePoint data analytics platform to achieve these goals.
Travis Johnson, Garmin Health global product lead, stated that “[c]ombining the sensor data from Garmin wearables with the data capture and analytical expertise of the ActiGraph platform creates a powerful solution for many different patient monitoring applications.”
ActiGraph chief technology officer Jeremy Wyatt expressed similar praise for ActiGraph’s new partner, stating that “Garmin wearables produce high resolution, accurate data streams that are ideal for scientific analysis and can provide additional, novel endpoints to the ActiGraph software platform.”
Garmin International, Inc. is a subsidiary of Garmin Ltd. Garmin is known for developing a variety of products, such as handheld GPS devices and wearable fitness trackers. On the other hand, ActiGraph offers a variety of activity monitors and also software platforms to analyze data collected by such monitors.
Both Garmin and ActiGraph acknowledge the growing importance of wearable devices as potential health and medical tools. By partnering with ActiGraph, Garmin has indicated its interest in the future development of wearable devices with medical applications. Likewise, the partnership allows ActiGraph to utilize Garmin’s experience in developing wearable devices to apply and hone its data monitoring and management systems.
On November 9, 2018, Cook Medical LLC filed a petition with the Patent Trial and Appeal Board requesting inter partes review (IPR) of U.S. Patent No. 6,306,141, assigned to Medtronic Vascular, Inc. The ‘141 Patent is entitled “Medical Devices Incorporating SIM Alloy Elements.” The ‘141 Patent states that it relates to “a medical device containing a shape memory alloy element.”
The ‘141 patent discloses using stress and temperatures below body temperature to restrain a metal alloy. The alloy expands to its original shape after being released from its restraint and exposed to body temperature. In one example, the ‘141 Patent describes that the disclosed device enables doctors to treat damaged or diseased heart valves with a less invasive transcatheter heart valve procedure. Figures 3 and 4 of the ‘141 Patent, shown below, illustrate a “side elevation view of a partial section of a catheter” in stressed (Figure 3) and unstressed (Figure 4) configurations.
The petition seeks to review all claims of the ‘141 Patent. Cook Medical’s petition submits two grounds on which the claims of the ‘141 Patent should be found invalid due to obviousness. The status of the proceeding can be examined by searching for the patent on the Patent Trial and Appeal Board website.
This is not the first time that the ‘141 patent has been subject to a petition for inter partes review. On January 17, 2014, Edwards Lifesciences Corporation filed a petition with the Patent Trial and Appeal Board requesting inter partes review of the patent for review of all claims of the ‘141 Patent. According to a Medtronic press release, on May 20, 2014, Medtronic and Edwards reached a “global settlement agreement” to “dismiss all of the pending litigation matters and patent office actions between them.”
In May 2013, Lombard Medical filed a petition for inter partes review of Claims 1-10 and 18-22 of the ‘141 Patent. Lombard Medical’s products, according to its website, include the AORFIX™ endovascular stent graft. According to a Lombard press release, on October 17, 2013, Lombard was granted a non-exclusive license by Medtronic to the ‘141 Patent, and Lombard formally requested a withdrawal of its inter partes review petition with the USPTO.
The ‘141 Patent has also been previously litigated. The ’141 Patent, among others, was previously asserted by Medtronic against W.L. Gore & Associates, Inc. in 2006; Gore’s EXCLUDER® AAA, TAG, and VIABAHN SFA® endoprosthesis devices were at issue. The parties entered into a confidential settlement in 2009.
Medtronic also previously asserted the ’141 Patent, among others, against AGA Medical in 2007. AGA’s AMPLATZER® Septal Occluder, Duct Occluder, and Vascular Plug devices were at issue. The parties entered into a settlement in 2010 in which AGA received a non-exclusive license to patents including the ’141 Patent in exchange for $35 million. AGA Medical was subsequently purchased by St. Jude Medical in October 2010 for $1 billion.
On December 10, 2018, the U.S. Food and Drug Administration (FDA) announced that it granted clearance of the reSET-O™, a mobile medical application to help increase retention of patients with Opioid Use Disorder (OUD) in an outpatient treatment.
Developed under an agreement between Pear Therapeutics and Sandoz Inc., a division of Novartis, reSET-O™ is said to be the first FDA-cleared Prescription Digital Therapeutic (PDT) for patients with Opioid Use Disorder. It is a mobile device application that provides a 12-week interval PDT for patients with OUD. Utilizing Community Reinforcement Approach (CRA), reSET-O™ provides a series of training, monitoring, and reminder tools and/or lessons for patients and health care providers alike. A clinical trial sponsored by National Institute of Drug Abuse (NIDA) found statistically significant increase in patient retention in a treatment program for 12 weeks who used the reSET-O™ program.
President and CEO of Pear Therapeutics, Corey McCann, M.D., Ph.D, reiterated the importance of the FDA clearance of the reSET-O™ for treating patients with OUD.
Nearly 50,000 drug overdose deaths involving opioids . . . took placed in the U.S. in 2017. Thereis an urgent need for new and innovative therapeutics to address this public health epidemic. This groundbreaking decision by the FDA ushers in a new standard for treating patients with Opioid Use Disorder and it signals a new path for therapeutic software to be used in conjunction with pharmacotherapy to improve efficacy.
FDA Commissioner Scott Gottlieb, M.D. addressed the FDA’s continued commitment to promote the development of medical device that could help treat addiction:
As part of our efforts to address the misuse and abuse of opioids, we’re especially focused on new tools and therapies that can help more people with opioid use disorder successfully treat their addition. Medical devices, including digital health devices like mobile medical apps, have the potential to play a unique and important role in contributing to these treatment efforts.
Sandoz, per the terms of the agreement, has already launched reSET®, Pear’s PDT for the treatment of Substance Use Disorder, in November 2018 and plans to launch reSET-O™ soon.
Recently, the U.S. Food & Drug Administration (FDA) announced plans to modernize FDA’s 510(k) clearance pathway, which was adopted more than 40 years ago. The FDA stated that the plans are aimed at continuing to ensure that new and existing devices meet their standard for safety and effectiveness as technology rapidly advances.
The FDA announcement reflects its focus on innovation by driving innovators toward reliance on more modern predicate devices. Under the current framework, medical device manufacturers are required to submit a premarket notification to demonstrate that the low- to moderate-risk device to be marketed is safe and effective by proving substantial equivalence to a legally marketed device (“predicate device”) that is not subject to Premarket Approval. According to the announcement, nearly 20 percent of current 510(k)s are cleared based on a predicate that’s more than 10 years old, contrary to the Agency’s belief that newer devices should be compared to the benefits and risks of more modern technology.
The Agency announced that it is considering, in the next few months, publishing on CDRH’s website those devices that have been cleared on the basis of demonstrated substantial equivalence of predicate devices that are more than 10 years old. The Agency also said that they are developing proposals to potentially subset certain older predicates and promote the use of more modern predicates. Following up on the announcement, FDA Commissioner Scott Gottlieb, M.D., stated,
As devices become increasingly complex, it’s important that they meet the latest standards for cybersecurity, interoperability, biocompatibility and usability engineering. The FDA has recently advanced policies on these issues, and we know that older predicates often don’t meet our more recent expectations.
Even though the announcement lacks details on these proposals, according to the announcement, in early 2019, the FDA intends to finalize guidance establishing an alternative 510(k) pathway that allows manufacturers of certain well understood device types to rely on objective safety and performance criteria to demonstrate substantial equivalence as a way to make it more efficient to adopt modern criteria as the basis for the predicates that are used to support new products.
Atrial fibrillation (AF), a common heart rhythm disorder, is often treated with cardiac ablation. Cardiac ablation uses RF (heating) or cryothermal (cooling) energy to scar the areas of the heart muscle that are responsible for the abnormal heart rhythm. Abbott Laboratories, Boston Scientific, and Biosense Webster (a subsidiary of Johnson & Johnson), each offer RF ablation catheters. According to one analyst, however, Medtronic is the first company to launch a cryoablation device and currently has reign over the cryoablation market. Recent developments suggest competition in cryoablation is now ramping up.
“The cryoablation market is set for disruption as Adagio Medical, Boston Scientific and a number of other smaller companies enter the space to challenge the market dominance of Medtronic’s devices.” -Sheryl Tang, senior analyst for medical devices at GlobalData.
GlobalData estimates cryoablation catheters make up approximately 27% of the global electrophysiology ablation catheters market, with the cryoablation catheter market growing at a Compound Annual Growth Rate (CAGR) of 5%. GlobalData expects small companies with successful devices in the cryoablation space to be prime acquisition targets for large companies looking to obtain a place in the cryoablation market and to secure a stronger position in the wider electrophysiology ablation market.
Laguna Hills, California-based Adagio Medical, Inc., appears to be one such small company with a cryoablation device. The company recently announced that it successfully treated its first patients with its One Shot+™ catheter. Adagio Medical describes its cryoablation platform as using continuous and uninterrupted flow of the cryogen through the catheter, allowing ultra-low temperature cryoablation catheters with diameters smaller than 2 millimeters.
In July of this year, Boston Scientific announced a definitive agreement to acquire Cryterion Medical Inc., a privately-held company developing a single-shot cryoablation platform for the treatment of AF. According to a recent article, the Cryterion cryoablation system uses a balloon catheter, mapping catheter, and steerable sheath. The Cryterion cryoablation system is not available for sale. However, a clinical study of the Cryterion cryoablation system is reportedly being conducted in Europe, with a CE Mark submission expected in early 2019. Boston Scientific plans to submit an investigational device exemption (IDE) application to the U.S. Food and Drug Administration (FDA), with patient enrollment expected to begin in 2019.
It remains to be seen whether Biosense Webster or Abbott Laboratories has interest in acquiring a company in the cryoablation space. If either company decides to do so, Adagio Medical may be a target for acquisition.
Abbott announced on October 19, 2018 that its HeartMate 3 Left Ventricular Assist Device (LVAD) has received U.S. Food and Drug Administration (FDA) approval as a destination therapy for people living with advanced heart failure. Physicians now can offer the HeartMate 3 system to patients not eligible for a transplant. The HeartMate 3 LVAD can serve as a permanent implant, allowing patients to live with the device for the rest of their lives.
The MOMENTUM 3 study, which included more than 1,000 patients with New York Heart Association (NYHA) Class IIIB or IV heart failure and which followed patients for a short-term endpoint of six months and a long-term endpoint of two years, supported HeartMate 3’s FDA approval. It was reported that during the study, patients with the HeartMate 3 LVAD had a survival rate of 82.8 percent at two years. It was also reported that the rate of suspected pump thrombosis (clotting of blood) remained low, at 1.1 percent, at two years and that the stroke rate was low, at 10 percent, at two years.
According to Abbott, the HeartMate 3 uses magnetic levitation technology. This technology has been designed to reduce trauma to the blood passing through the pump.
The U.S. Food and Drug Administration recently announced approval for Bose to market their Bose Hearing Aid. According to the press release, the Bose Hearing Aid, which was approved through the FDA’s De Novo premarket review pathway, is the first approved hearing aid that can be self-fit and adjusted by a user.
Malvina Eydelman, M.D., the Director of the Division of Ophthalmic, and Ear, Nose, and Throat Devices at the FDA’s Center for Devices and Radiologic Health commented:
“Today’s marketing authorization provides certain patients with access to a new hearing aid that provides them with direct control over the fit and functionality of the device. The FDA is committed to ensuring that individuals with hearing loss have options for taking an active role in their health care.”
According to the press release, clinical studies found the self-fitting Bose Hearing Aid to yield comparable outcomes relative to those found using a professional fitting. The press release also reported that users generally preferred self-adjusted settings over those selected by a professional.
In a statement made to TechCrunch, Joanne Berhiaume, a spokesperson for Bose, stated:
“Now, the De Novo grant by the FDA validates that Bose technologies can be applied to help people with mild to moderate hearing impairment take control of their hearing. We look forward to bringing affordable, accessible and great sounding solutions to the millions of people who could benefit from hearing aids but don’t use them.”
The U.S. Food and Drug Administration (FDA) announced an agreement with the U.S. Department of Homeland Security (DHS) to strengthen the partnership between the agencies and “stay a step ahead of constantly evolving medical device cybersecurity vulnerabilities.”
The agreement formalizes a long-standing relationship by developing a new framework for greater coordination and cooperation. As part of the new framework, specific responsibilities have been assigned to the FDA and the National Protection and Programs Directorate (NPPD), a component of the DHS. The following table provides a breakdown of the responsibilities outlined in the agreement:
|FDA Responsibilities||NPPD Responsibilities|
|1. Coordinate and participate in regular, ad hoc, and emergency coordination calls to enhance mutual awareness of vulnerabilities and threats||1. Serve as central medical device vulnerability coordination center|
|2. Provide NPPD with draft public releases to facilitate coordination of messaging||2. Participate in regular, ad hoc, and emergency coordination calls with FDA to enhance mutual awareness of vulnerabilities and threats|
|3. Comment in a timely manner on NPPD draft advisories and alerts||3. Confer with entities providing sensitive information prior to sharing any CCI, trade secret, or PCII-protected vulnerability or product information with the FDA|
|4. Assess the risk to health and patient harm when potential impact is disputed||4. Coordinate with FDA on the content of alerts and advisories to be published by DHS|
|5. Submit requests to NPPD for independent third-party technical assistance to analyze and test medical systems||5. Maintain technical capabilities to support requests for independent third-party analysis regarding the impact of vulnerabilities|
|6. Share non-trade secret information to resolve disputes of risk, impacts, and communication||6. Publish healthcare and public health related alerts and advisories|
In summary, the DHS will serve as the central coordination center and interface with appropriate stakeholders, and the FDA will provide technical and clinical expertise regarding medical devices.
FDA Commissioner Scott Gottlieb, M.D., during his discussion of the new agreement, addressed the FDA’s continued commitment to confront cybersecurity risk, while also recognizing the need for increased coordination between government agencies:
The FDA has been proactive in developing a robust program to address medical device cybersecurity concerns . . . But we also know that securing medical devices from cybersecurity threats cannot be achieved by one government agency alone. Every stakeholder has a unique role to play in addressing these modern challenges. That’s why this announcement is so important.
This agreement is not the first time a government agency has reached out to the FDA in an effort to strengthen medical device cybersecurity. As previously reported on the KnobbeMedical blog, the U.S. Department of Health & Human Services (HHS) Office of the Inspector General recommended earlier this year that the FDA include cybersecurity review as a greater part of the premarket review process for medical devices (e.g., through the inclusion of a Refuse-To-Accept checklists). This new FDA-DHS agreement is another example of continuing attempts to address ongoing medical device cybersecurity risks.
Best Practices, LLC recently released a study that provides insights into the amount of resources pharmaceutical and medical device companies allocate to ensure their products meet quality and regulatory standards. The study includes aggregate and anonymized data from 31 large medical companies, including Fisher & Paykel Healthcare, ResMed, Smith & Nephew, and Medtronic, among others. The majority of the surveyed companies operate primarily in the medical device field, but the data also includes results from diagnostic and pharmaceutical companies.
According to Best Practices, the study benchmarks the amount resources spent on quality assurance systems, regulatory affairs, and post-market surveillance of products. One exemplary finding was that, for the average company, the resources expended on the combined quality and regulatory systems amounted to nearly 8% of all company FTEs (full-time employee equivalence). The report further observes that more resources should be spent on the quality assurance system as company revenues increase to maintain consistent quality practices during expansion of operations.
Other sections of the report include data and analysis regarding the particulars of quality assurance systems including the number of CAPAs, NCEs, field actions, change requests, and FDA warning letters reported by individual companies. The study also includes data on the volume and duration of complaints received through post-market surveillance and benchmarks the amount of employee time spent addressing theses complaints.
The complete study is available for purchase through Best Practices, LLC.
The Food and Drug Administration (FDA) recently unveiled the Quality in 510(k) (“Quik”) Review pilot program, aimed at reducing the time it takes to review moderate-risk medical devices by one-third. The pilot, dubbed as “a Turbo Tax for information submitted in 510(k)s,” by FDA Commissioner Scott Gottlieb, will allow device manufacturers to submit premarket notifications electronically using “eSubmitter” software, as long as the device is classified under one of the specific product codes included in the pilot program and is not a combination product. In addition to lower risk devices, the pilot program includes some higher risk Class II devices, such as surgical lasers, certain endoscopic equipment, and certain imaging devices (e.g., MRI and stationary X-rays).
The FDA’s stated goal is to review 510(k) applications for devices that meet the eligibility requirements within 60 days, rather than the typical 90 days for traditional applications.
FDA Commissioner Scott Gottlieb also commented:
“As technology evolves, patients have the opportunity to access more innovative medical devices that can help improve their health. To advance that progress, the FDA must also modernize its own review and submission process to make sure that our programs continue to be efficient, consistent and scientifically rigorous.”
Since its first release in 2015, the Apple Watch has continued to evolve and incorporate more health- and fitness-tracking capabilities. The latest version of Apple’s Watch—Series 4—features a larger display screen, thinner case, a new interface, and, according to Apple “revolutionary health capabilities.” These health capabilities include electrocardiogram (ECG) functionality, which has been granted approval by the U.S. Food and Drug Administration. Also incorporated into the latest version of the Watch, according to Apple, are a new accelerometer and gyroscope that allow for fall detection.
Jeff Williams, Apple’s chief operating officer, stated:
The completely redesigned Apple Watch Series 4 continues to be an indispensable communication and fitness companion, and now with the addition of groundbreaking features, like fall detection and the first-ever ECG app offered directly to consumers, it also becomes an intelligent guardian for your health.
Apple notes that its Series 4 Watch allows wearers to place their finger on a dial for 30 seconds and receive a heart rhythm classification, which can identify if the wearers’ heartbeat is following a normal or irregular pattern. Irregular heart beat patterns, often referred to as Atrial fibrillation, increase the risk of heart complications. Recordings of such heart rhythm information are stored in a Health app and can be shared with physicians via a PDF file.
Some commentators believe the fall detection capabilities of Apple’s Series 4 Watch may prove significantly valuable, especially for elderly wearers. The Series 4 Watch is said to incorporate a new accelerometer and gyroscope which measure up to 32 g-forces and utilizes “custom algorithms to identify when hard falls occur.” The Watch also analyzes trajectory of the wearer’s wrist and the impact of accelerations, and sends an alert to the wearer after a fall event. Such alert can be dismissed or used by the wearer to make an emergency call to a healthcare provider. According to Apple, if the Watch senses a lack of movement for one minute after the alert notification, an automatic emergency call is made and a message is sent to emergency contacts along with location data.
The FDA recently announced its approval of GW Pharmaceutical’s Epidiolex drug, described as the first ever plant-derived cannabinoid medicine in the United States. The announcement notes that Epidiolex contains a highly purified form of cannabidiol (CBD), one of many cannabinoids derived from cannabis plants. CBD, however, lacks the psychoactive properties of its more famous cousin, tetrahydrocannabinol (THC). The FDA approved the use of Epidiolex for the treatment of seizures associated with several rare forms of epilepsy in patients 2 years and older.
According to public databases, GW Pharmaceuticals is the listed assignee of seven issued patents for methods of treating various epileptic and other medical conditions using CBD, as well published filings in Europe, Canada, Japan, and the United Kingdom.
Although CBD is an active ingredient of an FDA approved drug, CBD is still considered a Schedule 1 controlled substance under the federal Controlled Substances Act and cannot yet be placed for sale on the market. As a part of its approval of Epidiolex, the FDA has sent a recommendation to the Drug Enforcement Agency to reschedule CBD to a less-controlled schedule. The DEA must act on this recommendation within 90 days of the original approval, although the DEA is not under any obligation to reschedule marijuana or any of its components, including CBD. Nevertheless, observers have noted that the FDA’s approval of a CBD-based drug is at odds with the requirement that a Schedule 1 substance have “no currently accepted medical use in treatment.”
In a press release issued the same day as the approval of Epidiolex, the FDA Commissioner Scott Gottlieb, M.D. stressed that the approval was not a recognition of cannabis or any of its components as medicines. The press release notes that approval of Epidiolex was based on controlled clinical trials evaluating a highly purified form of CBD for treatment of specific conditions, manufacturing under consistent quality controls, and the creation of a reliable dosage form. Nevertheless, the Commissioner encouraged continued clinical research into cannabis related drugs and noted programs and guidances intended to facilitate and expedite development and review of drugs to address unmet medical needs.
On September 12, 2018, Apple released its new Apple Watch Series 4 with a new ECG app that can take an electrocardiogram (ECG). Apple’s new Apple Watch Series 4 has been granted De Novo classification by the FDA, which allows Apple to provide its Series 4 Apple Watches as an over-the-counter ECG-monitoring device.
Jeff Williams, Apple’s chief operating officer, noted Apple’s continued desire to make Apple Watch a more useful healthcare device for the public:
“The completely redesigned Apple Watch Series 4 continues to be an indispensable communication and fitness companion, and now with the addition of groundbreaking features, like fall protection and first-ever ECG app offered directly to consumers, it also becomes an intelligent guardian for your health.”
According to Apple, Apple Watch Series 4 is designed to intermittently analyze heart rhythms in the background and look for any irregular heart rhythm, such as atrial fibrillation (AFib). If a user’s heart rate exceeds or falls below a specified threshold, Apple Watch Series 4 can generate an alert. Electrical impulses are analyzed to generate ECG waveform and to determine AFib classification, which are automatically stored in Apple Watch’s Health app.
AliveCor received FDA clearance for its KardiaBand application for use with the Apple Watch last November. KardiaBand’s press release indicates that it includes a wearable band and a monitoring system integrated to Apple Watch.
However, according to The Verge, there are some important caveats to the FDA’s grant of de novo classification. First, both the ECG app and the irregular rhythm notification feature are not intended for people under the age of 22. Second, the irregular rhythm notification feature is not intended for people who have previously been diagnosed with atrial fibrillation. Moreover, the FDA does not intend to replace existing diagnostic methods and treatments for atrial fibrillation with Apple Watch. The FDA clearly states that “the feature is not intended to replace traditional methods of diagnosis or treatment.”
The FDA has announced new goals to help modernize its procedures and respond to new technologies. In a blog post by FDA Commissioner Scott Gottlieb, M.D., the agency expressed new priorities to help modernize clinical trials for medical devices and develop standards for new technologies like artificial intelligence.
According to Gottlieb, clinical trials “are becoming more costly and complex to administer” while “new technologies and sources of data and analysis make better approaches possible.” In order to take advantage of these better approaches, Gottlieb pointed to the FDA’s Breakthrough Devices Draft Guidance, which proposes streamlined procedures to develop flexible clinical trial designs for important medical devices. This will allow the FDA to “evaluate . . . innovative devices more efficiently.” Six breakthrough devices have already been cleared using this program.
Additionally, Gottlieb discussed the FDA’s new goal of enabling the use of “real-world evidence” to support decisions to approve devices. According to Gottlieb, “[r]eal world evidence can help answer questions that are relevant to broader patient populations or treatment settings where information may not be captured through traditional clinical trials.” The FDA is helping to design several proof-of-concept trials that utilize real-world evidence.
Finally, Gottlieb discussed the FDA’s role in dealing with new and emerging technologies. In particular, Gottlieb discussed artificial intelligence, which “holds enormous promise for the future of medicine.” Medical artificial intelligence models are currently in development and the FDA recently approved an AI algorithm for detection and treatment of distal radius fractures. According to Gottlieb, the FDA is exploring ways to handle and evaluate the kinds of data that are relevant to AI performance and safety, hoping to “enable a transparent benchmarking system for AI algorithm’s performance.”
Gottlieb concludes that the FDA has “undertaken a comprehensive effort to make sure that our organization and policies are as modern as the technologies we’re being asked to evaluate, and that we’re able to efficiently advance safe, effective new innovations.”
According to the press release, the BrainsWay Deep TMS system was previously cleared for treatment-resistant major depressive disorder in 2013, and this month’s de novo clearance is the second indication granted for the device, and marks the first clearance of a non-invasive device for treatment of OCD. The BrainsWay press release further notes that the Deep TMS system’s H7-coil targets the anterior cingulate cortex, which is known to play a role in the pathophysiology of OCD. BrainsWay stated that Deep TMS treatment, which uses changing magnetic fields to stimulate nerve cells in the brain, is non-invasive and has been shown to be safe and well-tolerated by patients.
BrainsWay plans to offer its OCD treatment both in new installations and as an upgrade to its existing systems. Addressing the broad future applicability of the Deep TMS system, BrainsWay president and CEO Yaacov Michlin said:
This clearance further establishes Deep TMS as a platform technology that will provide treatments for additional psychiatric indications, subject to successful completion of our currently ongoing multi center studies and regulatory approvals.
The United States Food and Drug Administration recently announced approval for Teva Pharmaceuticals to market generic epinephrine autoinjectors. According to the press release, Teva’s autoinjectors are the first generic versions of Mylan’s EpiPen® and EpiPen Jr ® to receive FDA approval.
Food Allergy & Research reports that as many as 15 million people in the U.S. have food allergies, which results in about 200,000 needing emergency medical care per year. Commenting on the approval, U.S. FDA Commissioner Scott Gottlieb stated:
This approval means patients living with severe allergies who require constant access to life-saving epinephrine should have a lower-cost option, as well as another approved product to help protect against potential drug shortages.
Analyst reports indicate wholesalers are not expecting to receive the generic epinephrine autoinjectors from Teva for several months. A Teva spokesperson commented that the company “is applying its full resources to this important launch in the coming months and is eager to being supplying the market.” Currently, Mylan’s EpiPen® 0.3 mg autoinjector 2-pack sells for about $697 at HealthWarehouse.com. Teva has not yet indicated the price of its generic autoinjector.
In a recent report, the U.S. Department of Health & Human Services (HHS) Office of the Inspector General (OIG) recommended that the U.S. Food & Drug Administration (FDA) include cybersecurity review as a greater part of the premarket review process for medical devices. In particular, the report suggests including cybersecurity documentation as a criterion in the FDA’s Refuse-To-Accept (RTA) checklist, using presubmission meetings to address cybersecurity questions, and including cybersecurity as an element of the FDA’s Smart template.
The FDA has been ramping up its cybersecurity review lately to deal with increased cybersecurity concerns. For example, a ransomware attack caused an Indiana hospital to shut down its system. Other cyberattacks may have gone undetected.
Currently, the FDA reviews documentation that manufacturers submit regarding cybersecurity as part of the premarket submissions. The FDA uses this information to consider known cybersecurity risks and threats when reviewing submissions that deal with networked medical devices. The FDA may request additional information from applicants when submissions require clarification or when cybersecurity documentation is lacking. In view of these requests, the FDA regularly approves manufacturers on cybersecurity issues when sufficient documentation is provided.
For example, in one review of a glucose monitoring system, an FDA reviewer did not find “any information on how the manufacturer included cybersecurity in the device’s design,” according to the report. “The FDA reviewer explained that the device relied heavily on users to protect against cybersecurity threats by using antivirus software and enabling firewalls. The FDA reviewer requested that the manufacturer update its hazard analysis to address the missing information. The manufacturer did so, and FDA found the update to be acceptable.”
Because of examples like this, the report suggests using cybersecurity documentation as an element in the FDA’s RTA checklist. The RTA checklist is a screen against incomplete applications. Were cybersecurity part of these checklists, failure by a manufacturer to provide adequate cybersecurity documentation could prevent the FDA to accept the submission for substantive review.
The report also suggests that the FDA use presubmission meetings to address cybersecurity-related questions. These meetings serve as a way for manufacturers to ask the FDA specific questions, such as whether the submission satisfies the FDA’s standards. During these meetings, the FDA can include cybersecurity as part of the discussion, which may reduce the amount of time for the FDA review.
Finally, the report recommended that cybersecurity be a stand-alone element in the FDA’s Smart template. A dedicated section on cybersecurity could allow FDA reviewers to explain the results of their review regarding cybersecurity in a standard format.
The FDA has agreed with these recommendations and has begun taking steps to implement them, such as by including cybersecurity in the Smart template. The FDA also said that it “intends to update the RTA checklist and the accompanying guidance to specifically identify cybersecurity as an item in the checklist during the next update of these items.” The FDA is also currently considering new rules that may require submission of software as part of a premarket submission.