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Boston Sci Launches 4th Generation DBS System in Europe

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Boston Scientific is rolling out the fourth generation Vercise Genus Deep Brain Stimulation System in Europe. The Marlborough, MA-based company said it had received CE mark for the device and would have a limited market release.

The device features full-body MRI conditional. and Bluetooth capabilities across the portfolio.

Boston Scientific said the Vercise Genus System is indicated to treat the symptoms of Parkinson's disease (PD), essential tremor, and dystonia by delivering precisely targeted electrical stimulation in the brain designed to provide optimal symptom relief.

"For patients, the Vercise Genus DBS System continues the tradition of small, thin devices, and it provides Bluetooth programming which is important during times of social distancing," Maulik Nanavaty, senior vice president and president, Neuromodulation, Boston Scientific, said in a release. "Combined with the option of a 25-year rechargeable battery as well as the expanded MRI conditional feature available on our primary cell devices, patients can find the best option to suit their specific needs." 

Vercise received a nod from FDA in December 2017. The Vercise Genus DBS system isn’t approved or available for sale in the U.S.  

Unlike traditional DBS systems that are built from pacemaker technology, this device is modeled from cochlear implant technology and the precise stimulation of auditory nerves it uses to replicate hearing.

To help boost Vercise and its DBS offerings, Boston Scientific acquired Cleveland Clinic’s neuromodulation spinoff Intelect Medical for $78 million in 2011.

Webinar Series: Marketing and Exhibiting During a Crisis

Informa Markets Engineering, the leading B2B event producer, publisher, and digital media business for the world's $3-trillion advanced technology-based manufacturing industry, has teamed up with Competitive Edge, the expo industry leader with nearly three decades experience in developing and delivering custom exhibitor education, to offer a two-part webinar series designed to educate marketers and business leaders on the new world of virtual exhibiting, teaching participants how to take full advantage of the virtual event platform capabilities, as well as why and how to promote their participation to drive traffic. 

Both webinars are free to attend and can be viewed both live and recorded. Registration links along with timing are provided below.

Part 1 - Successfully Marketing, Selling & Virtually Exhibiting During a Crisis

Watch on-demand recording here.

Part 2 - Optimizing & Driving Traffic to YOUR Virtual Exhibit

Wednesday, October 14, 11:00 a.m. - 12:00 p.m. Pacific Time / 2:00 p.m. - 3:00 p.m. Eastern Time

Learn more and register for the complimentary webinar here.

 

Melissa Magestro, VP/Group Portfolio Leader, Informa Markets Engineering, answered a few questions for MD+DI in an exclusive interview on the inspiration behind the series, what attendees will learn, and why virtual exhibiting is here to stay.

MD+DI: What was the inspiration behind the webinar series?

Magestro: Now five months into stay-at-home orders put in place in response to COVID-19, virtual events have become part of everyone’s new norm. In order to continue serving our medical design and engineering communities and keep our customers connected, we are building interactive virtual events where attendees and exhibitors can learn, discover new technologies, and connect with each other from the comfort of their homes or offices. Virtual events are different from live events though— and we want to help our customers be as successful as possible. So, these webinars are a way for us to provide strategies and tips that will help them get the most out of their investments in virtual events.  

 

MD+DI: What will each webinar cover?

Magestro: Our first webinar, “Successfully Marketing, Selling & Virtually Exhibiting During a Crisis,” is a complimentary all-new web-training session from tradeshow consultant Jefferson Davis, one of America’s leading experts on B2B marketing, sales, and exhibiting success. Davis focuses on why exhibiting virtually is an effective strategy, how to adjust your marketing and sales plans, critical success factors, and much more. This webinar will be helpful to any marketer or business leader whose company is participating in virtual events.

Our second webinar, “Optimizing & Driving Traffic to YOUR Virtual Exhibit” is a how-to webinar again presented by Davis, who will show participants how to optimize the core functionality of their virtual exhibit in the Swapcard platform, create an integrated marketing plan to drive traffic to your virtual exhibit before and during the event, and effectively interact with visitors to deliver value and capture leads. This is a must-attend webinar for marketers and business leaders who will be participating in Virtual Engineering Week.

 

MD+DI: What do you believe the future holds for virtual exhibiting? 

Magestro: This year has been one of change and adaptation for all industries. From an events standpoint, we made the decision to postpone many of our in-person events for the safety and wellbeing of our customers. We look forward to the day we can come back together as a community in person as nothing can replace the connections built and the value of in-person events and trade shows. However, we believe the future of our industry will be a hybrid of digital and in-person offerings. Expanding our digital and virtual offerings will enrich our live show experience, as well as help keep our communities connected all year-round. Thus, virtual conferences and exhibitions are here to stay.

Grail Hopes to Take Early Cancer Detection to New Level by Going Public

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Liquid biopsy specialist Grail is set to go public four years after it was spun out from Illumina. The Menlo Park, CA-based company is developing early cancer detection tests and has set a placeholder amount of $100 million for its IPO.

It should be noted that Grail is known for its exorbitant financings and has thus far brought in about $1.9 billion in venture capital funding.

The company previously raised $900 million in a Series B round and $300 million in an oversubscribed series C round. In May, the company raised $390 million for a series D round.

In a prospective filing, Grail announced potential launch plans for its products. Grail announced in May of last year that had been granted Break Through Device Designation for one of its tests.

“We plan to commercially launch Galleri in 2021 as a laboratory-developed test (LDT),” Grail said in a prospective filing. “In addition to Galleri, we are utilizing our proprietary technology platform and population-scale studies from which Galleri was developed to introduce additional products that address significant unmet medical needs, including a diagnostic aid for cancer test (DAC). DAC is designed to accelerate diagnostic resolution for patients for whom there is a clinical suspicion of cancer. We plan to commercially launch DAC after Galleri in the second half of 2021 as an LDT. We are also developing a minimal residual disease (MRD) test, designed to enable blood-based detection with or without tissue, and without the need for a personalized assay, as well as other post-diagnostic applications.”

The company hit a milestone in February when it initiated the PATHFINDER multi-center study. PATHFINDER marked the first time Grail’s test results will be returned to healthcare providers and communicated to participants to help guide appropriate diagnostic workups for more than 50 cancer types.

Grail isn’t the first high-profile liquid biopsy company to go public. Guardant Health went the public route raising $360 million in an offering.

Most recently the Redwood City, CA-based company, known mostly for its cancer detection efforts, altered focus a bit and developed a test for COVID-19. The company also won a nod from FDA for the Guardant360 CDX, a first liquid biopsy test for comprehensive tumor mutation profiling across all solid cancers.

 

Chembio Gives COVID-19 Antibody Testing Another Go

Image by ronstik - Adobe Stock COVID-19 antibody testing

As the old proverb goes, if at first you don't succeed, try, try again. Chembio Diagnostics is putting those words into action as the company pursues an emergency use authorization (EUA) for a new COVID-19 antibody testing system. Chembio says the new test, DPP SARS-CoV-2 IgM/IgG, provides results in 15 minutes from finger stick, venous whole blood, plasma, or serum samples.

The Medford, NY-based company was one of the first firms to get an EUA for an antibody test during the pandemic, and also was one of the first to have its EUA revoked by FDA due to performance concerns regarding the accuracy of the test. During the company's earnings call last month, Rick Eberly, Chembio's president and CEO, said the revocation had a significant negative impact on the company's product revenues and gross product margins in the second quarter and triggered a recall of unused tests from U.S. customers.

“We are pleased to have accomplished all of our objectives in the development and validation of the new DPP SARS-CoV-2 IgM/IgG test system,” Eberly said in a statement this issued week. “Submission of the EUA application for this test system has been the top priority for our organization because we understand there is a large need in the market for additional rapid tests – especially ones that offer the ability to decentralize testing locations. We are excited to offer a solution to patients and clinicians across the healthcare system that addresses these needs.”

Chembio says the new DPP SARS-CoV-2 IgM/IgG test system detects antibodies to the spike receptor-binding domain in the blood that the body produces in response to a COVID-19 infection. The test uses Chembio’s battery-powered Micro Reader 1 or Micro Reader 2 analyzers that are produced by Chembio Germany. According to the company, the DPP platform’s ability to "provide objective, numerical results can aid clinicians in avoiding the human interpretation errors associated with visual readings of traditional lateral flow tests."

COVID-19 antibody testing may assist clinicians in determining a patient's current or past exposure to the virus. The results and data from the test can contribute to improved clinical outcomes through the management of individual patients, as a population surveillance tool, and to potentially evaluate immune responses to anticipated vaccine administration, Chembio noted.

"We stand behind the real-world clinical data and performance of our original COVID-19 system," Eberly said during the Aug. 6 earnings call, according to Seeking Alpha transcripts. "...From the offset of the pandemic, we recognized our proprietary DPP technology could provide value across several COVID-19 related testing applications. The DPP technology in combination with our micro readers provides specific benefits that we believe make it well suited to point-of-care testing. The system is portable, provides accurate results in 15 minutes from finger stick blood or other samples, and is designed to detect multiple biomarkers simultaneously and discreetly."

Eberly went on to point out that the testing workflow is easy to use and scalable. He said clinicians can run multiple tests at the same time because test cartridges are only required to be inserted in the micro reader for 15 seconds to obtain results following the 15-minute test incubation period.

Also during the Aug. 6 earnings call, Eberly laid out the company's plans for leveraging Chembio's technology to develop a portfolio of COVID-19 tests. At that time, he said, Chembio was developing a revised DPP CPVOD-19 IgM/IgG system for antibody detection, and the DPP COVID-19 antigen system for viral protein detection. Further down the pipeline is a revised DPP COVID-19 IgM/IgG systems, a serology test for the detection of two types of COVID-19 antibodies.

Eberly said FDA identified new performance criteria in June that COVID-19 antibody testing systems must now meet to get an EUA.

"These defined standards have provided us with clarity and direction for our development objectives," he said. "The scientific and clinical knowledge base, along with our understanding of the virus and how it interacts with our technology, have both expanded significantly since our initial EUA was received. We are optimistic that with the clear definition of these requirements, combined with the expertise of our scientists and the flexibility of our platform, we can complete a revised system in a short period of time."

Medtronic Scores Breakthrough Designation for Transcatheter Tricuspid Valve

Image by Pixelbliss - Adobe Stock tricuspid valve

In the shadow of the wildly successful transcatheter aortic valve replacement (TAVR) market, the tricuspid valve was once viewed as the forgotten valve. That is quickly changing, however, as structural heart leaders like Edwards, Abbott, and now Medtronic are eagerly going after the transcatheter tricuspid valve replacement (TTVR) opportunity.

Medtronic reported on Wednesday that FDA has approved an early feasibility study of its Intrepid TTVR system in patients with severe, symptomatic tricuspid regurgitation, a disease in which the diseased, damaged or malfunctioning tricuspid valve allows blood to flow back into the heart's upper right chamber causing eventual heart failure or death. The study begins on the heels of a recent breakthrough device designation issued by FDA for the system. The Intrepid TTVR system is an investigational device worldwide.

Representing a large, unmet clinical need, tricuspid regurgitation affects more than 2 million patients in the United States, Medtronic noted. The disease is highly undertreated due to the morbidity and mortality associated with surgical intervention, the company said.

“The clinical experience generated during this initial study phase will be critical for the future of the therapy, as many of these patients are not good candidates for traditional surgical tricuspid valve interventions due to their poor right heart functions and are higher risk due to co-morbidities,” said Vinayak "Vinnie" Bapat, MD, chief of cardiothoracic surgery at the Minneapolis Heart Institute and co-principal investigator in the study. “We are optimistic that these early learnings will help fuel additional clinical research and device innovation around this treatable disease.”

Medtronic's Intrepid transcatheter valve is the same valve being evaluated for the treatment of symptomatic mitral valve regurgitation in the transfemoral mitral early feasibility study. The device is implanted using a transfemoral delivery catheter, which assists physicians in delivering and placing the valve through a catheter inserted in the femoral vein.

Others developing transcatheter tricuspid valve systems

In May, Edwards Lifesciences secured a CE mark for its Pascal transcatheter tricuspid valve repair system. The system is indicated in Europe for the percutaneous reconstruction of the tricuspid valve through leaflet repair by tissue approximation. The clasps and paddles gently grasp the leaflets to facilitate coaptation, while the spacer is designed to fill the regurgitant orifice area and prevent backflow. The clasps can be operated independently to facilitate optimized leaflet capture and the implant can be elongated to a narrow profile, allowing for safe maneuvering in dense chordal anatomy.

In February, Cardiovalve obtained breakthrough device designation and FDA approval of a feasibility study for its transcatheter tricuspid valve replacement system. Cardiovalve was originally a part of Valtech Cardio, a company acquired by Edwards.

About a year ago, Abbott Laboratories launched a pivotal trial for its Triclip TR treatment system. Abbott also received a CE mark for the Triclip in April making it one of the first minimally invasive, clip-based tricuspid valve repair device to be commercially available in the world.

Verily Achieves Another Milestone in Battle Against COVID-19

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FDA has granted Verily Lifesciences emergency use authorization for pooled testing of COVID-19. The EUA is the latest part of a multi-faceted strategy the South San Francisco, CA-based company has employed in the war against the novel coronavirus.

Verily said the pooling refers to the process of combining multiple samples into a single test, which results in the conservation of reagents. 

When the expected rate of positive detection is low (i.e. the likelihood that an individual in the pool is infected is less than 10%), the pooling method requires ¼ to ½ the number of tests as standard PCR tests.

Verily said its investigations have determined that pooling is an effective model for testing that can efficiently scale with increasing demand without compromising performance.

In a blog entry, Verily said, “We have published a series of white papers that touch on a variety of topics related to the identification of COVID-19 infection, including explanations of Verily's high sensitivity and pooled COVID-19 testing approaches.”

The Alphabet Company and former life sciences arm of Google launched the Baseline COVID-19 Research Project earlier this year to get a better understanding of the virus. Verily said its initial focus would be on serology testing.  

And last month, Verily began a CLIA  Lab for COVID-19  testing in its journey to facilitate solutions for the virus.

The firm said the lab is being used by customers of Verily's Healthy at Work program, including Waymo and other customers near Verily's South San Francisco campus, and will continue to be an integral part of its COVID-19 initiatives.

Verily’s sibling company Google has been hard on the grind in its COVID-19 efforts. In May Google announced that - along with its rival Apple – launched the Exposure Notification technology which can inform someone if they may have come in contact with a person that was diagnosed with COVID-19.

However, the joint effort has been met with criticism specifically over both companies’ privacy rules surrounding the technology. Health officials have said the software won’t be useful because while it will notify smartphone users if they’ve come into contact with an infected person, it won’t share those locations.

 

Will Tibial Neuromodulation Turn the Overactive Bladder Market on Its Head?

Image by 9nong - Adobe Stock overactive bladder

Patients suffering from an overactive bladder are finally feeling seen.

In the past year, new competition in the sacral neuromodulation market has driven innovation in that space, both from incumbent Medtronic and from the challenger, Axonics. Now there's another company looking to tackle overactive bladder, but this newcomer isn't going after the sacral neuromodulation niche. BlueWind Medical is developing a device small enough to be implanted in the ankle that is powered by a wearable, rather than an implantable pacemaker-like device.

Based in Herzliya, Israel — with U.S. headquarters in Park City, UT — BlueWind Medical recently began enrolling patients in a pivotal study of its Renova iStim implantable tibial neuromodulation system for the treatment of overactive bladder after securing a conditional investigational device exemption from FDA.

BlueWind's tiny, battery-less, lead-less implant was designed to offer overactive bladder patients (primarily women, but the condition does affect about 30% of men) with a more patient-centric, home-based therapy option.

"The overactive bladder market is a really interesting one because it's really not viewed as a disease," CEO Dan Lemaitre told MD+DI. "If you look up overactive bladder it may be classified as an affliction. ... as a consequence, the vast, vast majority of patients are untreated."

The global overactive bladder treatment market is projected to reach $4.19 billion by 2022, according to a Markets and Markets report, but Lemaitre said the market potential is actually much larger than that because so many patients are in the "watchful waiting" camp.

"They've tried behavioral therapy, which means changing liquid intake, not drinking before you go to bed at night if you're leaking at night. They've tried the drugs, but the pharmaceuticals here, if you read the label, they reduce the number of leaks per day relative to the placebos by less than one leak per day, so they don't really have a profound impact, and there's side effects [so] most patients simply don't stay on their pharmaceuticals. If you have failed both behavioral and drug therapy, you are then eligible for third-line therapy."

Today, third-line therapy means sacral neuromodulation — either with Medtronic's system or Axonics' system — or botulinum toxin injection, better known as Botox. With bladder Botox, as it's called, a urologist injects Botox into the patient's bladder in an effort to help the muscles relax, which is thought to give patients more time to get to the bathroom when the need arises. The injections are done in the clinic, and most patients tolerate the injections well, according to Mayo Clinic.

"Botox definitely works," Lemaitre said. 

The drawback to bladder Botox, however, is that the treatment results only last about six months, and then additional injections are needed. It is not recommended for men with a risk or history of enlarged prostate, and it comes with the potential side effect of urine retention.

"So about 80% of the patients drop out of Botox therapy after about four years," Lemaitre said.

Sacral neuromodulation is considered the gold standard for third-line therapy, he said, but that therapy requires both a trial lead procedure to see if the patient responds to the therapy using an external device to power the lead, and then a second procedure for the final implant, assuming all goes well during the trial period.

The most obvious drawback to the sacral neuromodulation systems on the market today, as Lemaitre puts it, is "you would have a pacemaker in your butt for the rest of your life."

He also noted that there used to be a problem with leads getting fractured or migrating but improvements in the technology has dramatically reduced the rate of that happening.

"The bottom line here is sacral nerve modulation has been around for over 20 years, and it's probably penetrated 3% of the market. So I think patients have spoken," Lemaitre said. "They don't want to go through that invasive of a procedure ... they don't want to have a pacemaker in their butt, and they're certainly not looking for reinterventions down the road."

So what is the alternative?

"The Chinese figured out thousands of years ago that if you stick a needle in someone's ankle it has an impact on the bladder. You're probably thinking you failed physiology, but you didn't," Lemaitre said. "The reality is, there are signals that run from the tibial up toward the sacrum, and what you're doing with that therapy is basically trying to disrupt these inappropriate signals that the brain is getting from the bladder that says it's full when it's not."

In addition to the InterStim technology, Medtronic offers the Nuro system, which delivers percutaneous tibial neuromodulation (PTNM) to treat overactive bladder. It is an office-based treatment delivered with an external neurostimulator, and Lemaitre, who used to work at Medtronic, said the Nuro system has been proven to work in double-blind studies. The downside of this treatment option, he said, is that it requires weekly doctor visits for 12 consecutive weeks. PTNM has been around for about 10 years, he said, and is implanted in roughly 10,000 to 20,000 patients a year.

"It's just not a form factor that works," he said.

What is BlueWind's solution?

"What we've tried to do is create a tibial nerve stimulation system that is in a form factor that works for patients," Lemaitre said.

Image courtesy of BlueWind Medicaloveractive bladder

BlueWind's solution involves a small incision in the ankle to implant a 3-cm device that is then sutured in place to prevent the device from migrating. The device is been implanted in more than 70 patients between the company's pilot studies and now its U.S. pivotal study.

To power the device, the patient simply puts a small cuff around their ankle.

"It's really light weight," Lemaitre said. "If I was wearing it right now, I could be walking around, talking to you, [or] I could have my feet up. It's very forgiving in terms of positioning. You do feel the therapy, there's a tingling sensation when it's on, but it's very manageable and it's customized for the patient. You wear it for about 30 minutes a day."

In a commercialized setting patients might only use the device for 30 minutes every other day, or they might wear it every day for a full hour, depending on their individual needs. The system does have a feedback loop which is constantly interrogating the implant to make sure the patient is getting a therapeutic dose of energy so if the cuff isn't absolutely centered over the implant, they'll know to adjust it.

"We believe what we've been able to create here is a device that bridges this gap of patients who either are leery of doing something more invasive like sacral nerve modulation, but don't want to do Botox or are tired of Botox, and really being able to attract the vast majority of patients who are sitting in that watchful waiting camp," Lemaitre said.

What if it doesn't work for all overactive bladder patients?

"We sure don't believe we're doing a science experiment because it's a known mechanism of action, it's been proven to work in a different form factor, ... but let's say it doesn't work in a subset of patients. We've preserved all therapeutic options. You can do Botox, you can go on to do sacral nerve modulation, we can explant the device if people are concerned about having that tiny electrode left in their ankle."

Lemaitre also said the clinicians who have been involved with the company to date "are desperately looking for a solution for patients who simply aren't satisfied with first and second-line therapy and aren't ready for either of the available third-line therapies right now."

BlueWind's goal is to complete enrolment of the 200-patient trial within 18 months. The primary endpoint for the trial is six months, but FDA has asked for 12 months of follow up data to prove the safety and efficacy, especially because it is a single-arm study. It would be difficult to design a double-blind study around this particular therapy, Lemaitre explained, because the patient is able to feel the therapy in action. That puts the company on a trajectory to potentially secure FDA clearance sometime in the first half of 2023, he said.

FDA Wants Your Feedback

Image by gustavofrazao - Adobe Stock FDA seeks feedback from medical device manufacturers

FDA is building a web-based tracker that displays the progress of a medical device marketing submission throughout the agency's review process. The agency is accepting industry feedback between now and Oct. 8 on the features and information medical device companies would find useful in this tracker.

The tracker is being developed as part of FDA's committment to provide "a new information management system that provides an industry dashboard that displays near real-time submission status" to the medical device industry as part of its MDUFA IV commitments (see MDUFA IV Commitments letter, Section III.C: IT Infrastructure for Submission Management).

Using this tracker, a representative of the submitter's firm will be able to view the progress of its submission in a clear and concise format. Only the representative identified in the submission can access this protected information.

FDA asked the industry to consider the following when providing feedback on this tracker:

  • What information is most useful to you when you have a premarket submission under review and why?
  • What information or features would improve a challenge you currently have with the FDA review process for device marketing submissions?
  • What additional communication methods may be useful when receiving progress information from the FDA regarding device marketing submissions? Examples may include emails, text messages, data export tables, or application programming interfaces (APIs).

After the progress tracker is launched, FDA said there will be feedback methods available within the tracker itself to inform the design of future versions.

The agency said feedback may be provided anonymously. FDA is not requesting or collecting any identifying information and will not publish responses or reply to them.

To submit feedback, send an email to PremarketProgressTracker@fda.hhs.gov.

Medtech AI & Software Regulation in China: 5 Things to Know

Image by OpenClipart-Vectors from Pixabay Medtech AI and Software Regulation in China

COVID-19 has accelerated ongoing digital healthcare trends in China, presenting market opportunities for global medtech artificial intelligence (AI) and software players. But because the traditional life sciences regulatory frameworks in China were developed with hardware at front of mind, there is a regulatory lag as the frameworks catch up to the latest medical technology advances.

This article presents five regulatory issues relating to medical AI and software products in China for foreign developers/manufacturers.

1. Shift of emphasis to whole-of-lifecycle scrutiny from point-in-time registration.

China’s regulatory body for life sciences products, the National Medical Product Administration (NMPA), is a resource-stretched regulator that has traditionally approached safety regulation for health products from a gateway or point-in-time perspective. This meant traditionally that a lot of time and effort was incurred ensuring products met the requisite standards, but once market approvals were granted, there was little appetite for ongoing scrutiny.

Recent health scandals and convergence to world standards (China is a member of the International Medical Device Regulators Forum) within a backdrop of rapid technological advances in medical technology have proved the traditional rigid framework incomplete. The NMPA is undergoing a noticeable shift in regulatory philosophy from point-in-time to whole-of-life scrutiny.

The reasons for this are many. The unique difficulties associated with regulation of digital health products further accelerates demand for evolving regulatory frameworks. Because of the continuous nature of software development and because software updates can so readily be pushed out to the market, traditional regulatory frameworks that view any product change with scepticism—often requiring a timeline and submission process similar to a fresh premarket application—doom healthcare services to backward-facing solutions even as the available patient solutions proliferate. For AI products that change second to second as the product adapts to a variety of inputs, the challenge is even more acute.

But with a number of recent announcements and guidelines over the past few years, the NMPA has demonstrated a maturing approach. This has meant a step up in overseas factory inspections for medical device manufacturers that import to China—there were around 24 that we at Cisema were aware of in 2019—as well as the introduction of annual risk reporting, special device identifiers, and lifetime verification requirements.

The role of the NMPA Legal Agent, the key contact for the NMPA for each registered device, has correspondingly increased in importance. Like the European Union and United States, China requires a local entity before market clearance applications will be accepted, but this need not be the manufacturer itself. A local distributor (that will thereby tend to gain inordinate power over the foreign manufacturer) or a third-party service provider may also perform this role.

Historically a minor one, the role has expanding responsibilities as the primary NMPA contact for post-market surveillance (PMS) duties.

2. ‘Major’ vs ‘minor’ software updates and the regulatory implications

Software developers should also be aware of how a product change application works. The traditional China regulatory framework allows very few instances for a product to be amended without first obtaining approval from the regulator. One of software’s strengths is its iterative improvability, but from a regulatory standpoint this causes problems because of the potential for an unapproved change to lead to health safety or efficacy concerns.

The starting point is that a medical software update is read broadly to refer to any modification made by the manufacturer/developer to the software during the entire software lifecycle. 

Then, software updates are divided into ‘minor’ or ‘major’ updates. Minor updates are slightly enhanced or are corrective software updates such as improvements of computing speed, regular security patches, text modifications of the user interface, or similar. These should not affect the safety or efficacy of the product.

If a software update is minor, then it is managed through the company’s quality management system, and no prior approval is needed from the NMPA in order to make the change. This means that the relevant declaration materials will effectively be submitted for inspection by the NMPA together with the next registration filing, being a subsequent registration change or a registration renewal (every 5 years for Class II and Class III products in China).

But for major software updates, which include changes to operating systems, clinical functions (new operating modes or new core algorithms), software output changes, user interface changes, or other changes that may affect safety or effectiveness, a product change application will need to be submitted to the NMPA prior to rollout of the update. This can take 18 months from start to finish. There will also be fairly substantial application fees.

The document requirements for major software updates include basic information such as software identification, security level, structure function, hardware topology, operating environment, scope of application, contraindications, registration history, as well as implementation processes such as development overview, risk management, requirement specification, life cycle, verification and confirmation, defect management, update history, and clinical evaluation.

3. AI-focused special regulatory frameworks developing

What does this mean for software that changes second to second depending on inputs? AI devices are a ‘hot’ area in China (and globally) and have received encouragement from the very top levels of government in China’s most recent 5 Year Plan.

The NMPA has issued various guidelines relating to AI in catchup to the U.S. FDA, which approved an AI-based diabetes-related device in 2018. Most notably in June 2019, the NMPA issued “Technical Guideline on AI-Aided Software” in which NMPA clarified that for AI software, version naming rules should cover algorithm-driven and data-driven software updates and should list all typical scenarios for major software updates.

A presentation by the NMPA in September 2019 called “Introduction to Review Points for Decision-Making Medical Device Software Using Deep Learning Technology” further explained the system of AI-MD guidelines.

For AI-assisted devices, NMPA has again shown increasing maturity by recognizing that the risk-based method is the guiding principle in determining whether and when a product change needs to be filed. Total lifecycle management is also strongly emphasized as the regulatory method to monitor safety for users and NMPA has said AI products in particular will faced increased PMS scrutiny.

Therefore, whether AI medical software updates require product change approval depends on statistical significance. Where the software maintains its effect based on the original application, there will be no need to obtain pre-approval.

4. Fast track pathways are available but difficult to use

There are four broad fast-track pathways available for medical device approval in China.

  1. Innovative approval
  2. Priority approval
  3. Emergency approval
  4. Real-world data such as through Hainan Boao Lecheng Medical Tourism Zone or, in future, Hong Kong-Macau-Guangzhou Greater Bay Area.

None is straightforward, and very few overseas products—in the tens out of thousands registered in the last few years—have been able to take advantage of any of the fast-track pathways. If one of the first three statuses above is granted (which does not mean ‘approval’), the device or SaMD will be allocated priority throughout the registration process but will not be exempted from the regulatory requirements. In addition, a specially assigned NMPA officer will be allocated to provide guidance throughout the expedited process.

Innovative approval has a number of criteria to be satisfied, most relevantly that the product has significant clinical application value, a China patent, and no other similar products on the market in China.

Priority review relates, relevantly, to treatment of rare diseases with significant application value.

And emergency approvals are for public health crises, which was relevant earlier this year in response to the fight against COVID-19, but such applications have not been accepted for some months now.

Hainan Boao Lecheng Medical Tourism Pilot Zone (‘Pilot Zone’) has seen a flurry of publicity recently as part of a government-approved push to keep medical tourism within China, including presentations as recently as the August 14, 2020, webinar hosted by the China-Britain Business Council (CBBC). The Pilot Zone consists of a number of Chinese and foreign cooperative medical institutions within a roughly 20 square km area on Hainan Island, a large island off China’s south coast and the most southern province in China. If one of the hospitals in Boao Lecheng sees an unmet clinical need for your product, it may be imported and used in the zone without prior NMPA clearance or approvals. This allows the capture of real-world data on Chinese nationals and can support a subsequent application to China-wide market clearance. But it does not circumvent the need for a clinical trial.

Hong Kong Greater Bay Area is a recent draft development that will allow medical products approved in Hong Kong (a voluntary filing system) to be sold throughout certain healthcare institutions within the Greater Bay Area, an area with a population nearly that of Germany with 70 million people. This would similarly enable the collection of real-world data on Chinese nationals, which could usefully support a subsequent China-wide market approval application.

5. First AI medical device approved in China earlier this year

The NMPA announced earlier this year that it had approved the first Class III ‘AI’ medical device, DeepVessel FFR developed by Beijing Keya Medical to perform physiological functional assessment of the coronary arteries non-invasively. It extracts three-dimensional coronary tree structure and computes Fractional Flow Reserve (FFR) values in minutes from the coronary computed tomography angiography (CTA) scan, according to its website.

It was approved as an ‘innovative’ product, meaning it was able to take advantage of the innovative fast-track pathway referred to above. This was because no domestic product of the same variety had been registered and listed. At the time of NMPA registration, only one other similar product globally had been marketed (Heartflow in the United States). Compared with that products of the same variety, the performance index of this product was determined to be at the international leading level.

But DeepVessel FFR still required clinical trials as a Class III product. It conducted prospective clinical trials in 2017 and retrospective clinical trials in 2019 in support of its NMPA application, according to its website.

Since DeepVessel was approved, two other Class III AI medical devices have also been approved: a software for ECG analysis by Lepu (乐 普) and diagnostic software for MRI images of intracranial tumors from BioMind (安 德 医 智).

Conclusion

The recent flurry of Class III AI medical devices that have been approved for sale in China demonstrate that there is clear market opportunity for such products. COVID-19 has only served to accelerate digital innovation as China (and global) healthcare providers grapple with alternative methods to diagnose and treat patient ailments. But medical software and AI developers must be cognizant of the various regulatory hurdles.

References

Emily Rapalino, Cindy Chang, Nicholas Mitrokostas, “Patent and Regulatory Challenges in AI’s Use in Life Sciences” (July 1, 2020:  https://www.medtechintelligence.com/column/patent-and-regulatory-challenges-in-ais-use-in-life-sciences/ (Accessed 7 Aug 20)

NPC Decision “Decision of the State Council on Suspending the Implementation of the ‘Regulations on the Supervision and Administration of Medical Devices’ in the Boao Lecheng International Medical Tourism Pilot Zone, Hainan Province” issued 2 April 2018

China Britain Business Council & Hainan IEDB, “CBBC Hainan Free Trade Port Policy Webinar” (14 Aug 2020)

Keya Medical, “DEEPVESSEL FFR is Approved for Clinical Use in China” (published online 22 January 2020): https://www.keyamedical.com/deepvessel-ffr-approved-for-clinical-use-china/ (Accessed 2 September 2020)

NMPA, “Technical Guideline on AI-Aided Software” (June 2019)

NMPA, “Introduction to review points for decision-making medical device software using deep learning technology” (September 2019)

Medtech Materials: Ideas for Selection, Design, Processing, and Addressing Challenges

Brad Pict/Adobe Stock Images Medtech Materials Webinars

Materials selection for medical devices has always been a complex endeavor given safety and performance requirements. There may also be new demands such as enhanced performance, biocompatibility, microbial reduction, or other features. Design engineers also need to consider budgets and deadlines, which could impact development time.

To help medical device innovators select the right material and process for their next project, MD+DI will host a series of webinars beginning on September 22:

 

For instance, Mark Mielke, PhD, vice president of sales and marketing, Praxis Technology, will examine in the first webinar how titanium metal injection molding (TiMIM) could reduce the cost of titanium implantable products and might even improve performance. According to the company, TiMIM creates cost savings of more than 40% compared with CNC machining and provides very dynamic response to volume requirements.

Next, in the webinar, Solving Complex Device Design Challenges through Partnership, Justin Strike and Dan Sanchez, product managers with Trelleborg Healthcare & Medical, will share how experts in molding and extrusion could help R&D engineers optimize device design and eliminate challenges before they happen. They will share how an FEA analysis can be used to model performance prior to tooling investments and how Design for Manufacturing methodology can bring a device from prototype to serial production. They will also examine advancements in extrusion methods that could simplify device designs.

And in Designing with Silicones: The Solution to Your Medical Device Challenges, Alex Santayana, applications engineer for NuSil, will explore silicone’s capabilities as well as fabrication methods. He will also discuss the future of silicones and medical devices.

Join MD+DI September 22, 23, and 24 to hear these presentations and pose questions about your own challenges.