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.