FDA Pre-cert Program for Lab-Developed Tests

The FDA may begin certifying the laboratories that produce lab-developed tests (“LDTs”) instead of drafting regulatory rules to cover the tests themselves.  The American Clinical Laboratory Association describes LDTs as:

[T]ests that hospitals, academic, and clinical laboratories develop as testing services according to their own procedures.  These tests are often created in response to unmet clinical needs, and are commonly used for early and precise diagnosis, monitoring, and guiding patient treatment.

The organization believes that the ability to innovate and design custom diagnostic tests has been critical to the growth of personalized medicine and keeping pace with the changes in the medical profession.

According to Sean Khozin, associate acting director of the FDA’s Oncology Center of Excellence, the program will be modeled after the FDA’s pilot approval process for digital health products. This process functions as a stamp of approval by the FDA, Mr. Khozin explained that:

The precertification program represents a modern approach to regulation, shifting the focus from the product, to the developer of the product . . . .  That product then doesn’t necessarily have to go through analytical validation process.

This program may be compared to to the Digital Health Software Precertification (“Pre-cert”) Program that was announced in July, 2017.  The agency picked nine companies for the program, including Alphabet Inc. (Google’s parent company), Apple Inc., and Fitbit Inc. Under the Digital Health SOftware Pre-cert program, the FDA will examine the software (rather than the device itself) and inspect facilities to ensure they meets the FDA’s standards.  If the companies pass the audit, the companies will attain pre-certified status and their products will be pre-cleared in lieu of being examined by the FDA’s traditional regulatory framework.

Regulating LDTs has been an issue that the FDA has considered in response to a “boom” in the diagnostics industry and as more physicians demand complex tests to screen for diseases like breast cancer and Alzheimer’s.

The medical device and clinical laboratory industries have been at odds over the question of LDT regulation since 2014, when the FDA first sought to regulate LDTs.  Device makers supported the FDA’s regulation-based approach while clinical labs, which were already regulated by the Clinical Laboratory Improvement Amendments (CLIA) under the Centers for Medicare & Medicaid Services, disagreed.  The FDA dropped its enforcement proposals in 2016.  The American Clinical Laboratory Association, whose members traditionally have been regulated under CLIA, said:

[The ACLA] has consistently maintained that LDTs are not medical devices and cannot be regulated as such. The decision by the FDA last year to not issue final guidance to regulate LDTs was a victory for diagnostic innovation and for patients.

The FDA is now expected to announce a new pilot plan soon to certify laboratories that develop diagnostic tests in lieu of drafting rules for the tests themselves. The plan for the LDTs do not seem to conflict with CLIA rules as the CLIA rules does not concern manufacturers, the CLIA rules concern labs.

 

 

Medtronic Pain Management Device Approved by FDA

Medtronic announced FDA approval and U.S. launch of its Intellis Platform for the management of certain types of chronic intractable pain.  According to Medtronic, the Intellis platform features the world’s smallest implantable spinal cord stimulator (SCS), which includes an implantable pulse generator that looks like an older-style pacemaker, but with wire leads that delivers mild current to a spinal vertebra.  The Intellis, and other SCS systems deliver, neurostimulation at the spinal cords to prevent pain signals from reaching the brain.

The MIT Technology Review reports that SCS systems carry promise because they represent an alternative to opioid-based pain management.  It is estimated that more than 20,000 Americans a year die from overdoses of prescription pain drugs.  Government and industry alike recognize the gravity of the opioid issue. FDA Commissioner Dr. Scott Gottlieb has stated that opioid abuse is is taking a staggering human and economic toll and is therefore a top priority.  Industries are also responding with ever-improving SCS systems (Medtronic’s pain-therapies business show $825 million in revenue during the company’s 2017 fiscal year).

According to Medtronic, the Intellis system allows physicians to better address the subjective and personal nature of patient’s chronic pain.  Based on recorded and tracked patient activity, including body positions and how patients self-administer their therapy, Intellis allows a physician to program and manage pain therapy for each patient with a wirelessly connected Samsung tablet.

Samsung Chief Medical Officer Dr. Dave Rhew said:

We are excited to partner with Medtronic in their aim to simplify programming, and streamline therapy management with the Intellis platform . . . Samsung’s Galaxy tablets — secured by the HIPAA-ready Samsung Knox mobile security platform — will support future Medtronic therapies and over the air (OTA) software upgrades to ensure clinicians using Intellis have access to the most up-to-date solutions.

Medtronic is not the only industry player to explore cross-industry partnership: at least one of its competitors, Abbott (which acquired St. Jude and its line of chronic pain treatment devices in January, 2017) offers SCS devices featuring controllers made by Apple.

 

FDA Announces Plans for Alternative Clearance Pathway

The U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb recently announced that the agency plans to publish a draft guidance outlining a voluntary alternative pathway for new, moderate-risk devices for use in patient care.

According to Commissioner Gottlieb, the FDA regulatory processes for medical devices have remained relatively unchanged for over 40 years.  Under a commonly used clearance pathway, device manufacturers are required to submit a Premarket Notification, known as a 510(k).  The 510(k) constitutes a premarketing submission demonstrating substantial equivalence of a new device to a similar, legally marketed “predicate” device.  The FDA explains that the submission allows the FDA to determine whether the device is as safe and effective as an equivalent device already placed into one of the three FDA classification categories.

However, Commissioner Gottlieb believes that “there are an increasing number of cases where this basic framework isn’t well-suited to reflect the innovation that we see today in certain technologies, and how we must evaluate those technologies.” Similarly, he states that the current 510(k) requirements fail “to realize the full potential of the FDA’s consensus standards program, which was established through the Food and Drug Administration Modernization Act of 1997, and will be refined and expanded as a result of provisions in the 21st Century Cures Act of 2016.” To address these shortcomings, the FDA plans to offer an alternative pathway for demonstrating substantial equivalence in a 510(k) submission.

Under the new pathway, Commissioner Gottlieb states that manufacturers could obtain clearance without direct comparison testing to a predicate device.  Instead, substantial equivalence could be established by meeting objective safety and performance criteria, including FDA-recognized standards, FDA-developed guidance documents, or a combination of the two. The pathway would only be available for pre-specified categories of mature devices – those for which safety and performance criteria that meet or exceed the performance of existing, legally marketed devices can be identified.

Commissioner Gottlieb believes that this alternative pathway:

[H]olds tremendous promise to further streamline device review for sponsors and FDA and allow new innovations to get to patients more quickly; to allow more advanced technologies to be efficiently incorporated into new devices; and to foster greater confidence in the FDA’s ability to efficiently evaluate safety and benefits of technologies cleared under this pathway – all while maintaining the same gold standard that we apply to existing review processes.

The FDA will release its draft guidance on the new 510(K) pathway in the first quarter of 2018.

First-Ever De Novo Clearance by FDA’s Orthopedic Branch

According to IlluminOss Medical, Inc.’s recent press release, the company has successfully obtained the first-ever de novo clearance from the FDA’s Orthopedic Branch for its minimally invasive bone stabilizaion system (the “IlluminOss System”).  According to the FDA, the de novo clearance is reserved for new, novel devices whose type has not been previously classified.

IlluminOss, a privately held commercial-stage medical device company based in East Providence, Rhode Island, describes itself as being involved in the development and commercialization of minimally invasive fracture fixation techniques.  The company explains that the newly-approved IlluminOss Bone Stabilization System is used for the treatment of impending and actual pathological fractures of the humerus, radius, and ulna resulting from metastatic bone disease.

Traditional bone stabilization procedures utilizing invasive techniques and intramedullary rods can risk causing extensive soft tissue damage and reduced patient mobility.  Moreover, the metal plates and rods may increase patients’ risk of cortical porosis, delayed bridging, and refractures upon removal.  Regarding its IlluminOss System, IlluminOss states:

The IlluminOss System was developed with an aim to provide improved patient experiences and outcomes when treating pathologic fractures. There is a critical need to make less invasive orthopedic fracture repair options available to an aging and underserved market segment.

In contrast to traditional fixation techniques, the IlluminOss explains that its System uses a small-diameter PET balloon and visible light fiber, each of which may be threaded through a 4.5 mm pathway into the medullary canal through a small incision in the patient’s skin.  Once inserted, the PET balloon is filled with a photoactive liquid monomer, causing the balloon to expand and conform to the specific shape of the patient’s bone.  With the liquid-filled balloon in place, the photoactive monomer is polymerized utilizing the visible light fiber, resulting in a hardened implant which conforms to the patient’s specific bone structure within 90 seconds.  The hardened implant stabilizes the fracture by providing both longitudinal and rotational stability across the length of the implant.

The IlluminOss System has been available internationally since 2010.  IlluminOss reports success in international markets: surgeons have reported smaller incisions, shorter procedure times, and a faster return to the patient’s daily living activities.  Reduced complication rates, and shorter hospital stays have also been observed.

With marketing clearance in hand, IlluminOss plans to initiate U.S. commercialization efforts in the second quarter of 2018.

Report Finds European Union’s Assessment of High-Risk Medical Devices of Low Quality

A report appearing in the December 2017 issue of Value in Health, (a journal of the International Society for Pharmacoeconomics and Outcomes Research) concluded that assessments of high-risk medical devices in the European Union were of low quality – based on evidence from studies that were methodologically inadequate.

The authors of the report reviewed 1,376 health technology assessment reports (“HTAs”) of high-risk medical devices (“MDs”) that were filed between 2010 and 2015.  Of the 93 that were eligible for analysis, the researchers rated each of these studies on the following criteria:

  1. Evidence base
    • Was the evidence in the HTA based on submissions by the manufacturer, data identified by an independent source, or both?
  2. Type of evidence
    • Was the evidence in the HTA based on “direct” (e.g. head-to-head trials) or “indirect” evidence?
    • Direct evidence from well-conducted randomized controlled trials were seen as providing the most valid estimates regarding the effectiveness of competing health care interventions.
  3. Level of evidence
  4. Further considerations of scientific evidence
    • What were the total number of studies considered in each HTA report?

The report ultimately found that while almost all assessments considered “based their evaluation on direct evidence from independent systematic literature searches, good-quality data were scarce.”  The report further stated that “our findings illustrate that even if systematic reviews and RCTs [randomized controlled trials] were available for assessment, most of these studies showed an unclear or high RoB [risk of bias] according to the specific tools used in their reports.”

The report ultimately concluded that:

In the EU countries, MDs are essentially regulated in the same way they have been since the 1990s. This means that high-risk MDs can enter the market and be used in humans without the requirement of evidence from robust clinical studies. As a consequence, scientific evidence prior to market approval of high-risk MDs is often based only on evidence from studies that were methodologically inadequate.

In summary, the report proposed that “additional changes are necessary, specifically with regard to the marketing authorization process of MDs, with stricter quality requirements based on methodologically robust trials, possibly in combination with other evidence sources.”

Microbot Medical to Acquire CardioSert’s Technology

Microbot Medical Inc. announced that it entered into an agreement with CardioSert Ltd. to acquire CardioSert’s patented guidewire technology, including R&D information, technical know-how, and intellectual property.

Microbot expects the acquisition to close in April 2018, at which time Microbot expects to have a patent portfolio of 25 issued/allowed patents and 15 pending patent applications worldwide, including CardioSert’s one issued patent (U.S. Pat. No. 9,586,029) and three pending patent applications. According to CardioSert, CardioSert’s technology offers capabilities such as steering and adjustable stiffness to guidewires used in interventional cardiology, radiology and vascular surgery. These features give physicians the ability to control the tip curvature, to adjust tip stiffness in a gradually continuous manner, and to produce impacts with the tip for negotiating calcified segments.

Microbot believes the technology has uses in other spaces, including peripheral intervention, neurosurgery, and urology. Microbot also believes the technology, when added to its existing robotic capabilities, will be consistent with its strategy to develop micro-robotic technologies for surgeries utilizing the natural and artificial lumens in the human body, expand and enhance its intellectual property portfolio, and allow it to enter adjacent medical spaces and applications.

Microbot reports that CardioSert will receive 100,000 restricted shares of Microbot’s common stock, cash payments totaling $300,000 (including $50,000 paid at signing), the potential for future milestone payments based on development progress and regulatory approvals, as well as royalties from futures sales related to the technology.

Virtual Reality in Healthcare

Virtual reality is not just a growing trend in the entertainment industry, but is now reaching the healthcare field. As the technology improves and develops, the uses of virtual reality expand for doctors, students, and patients. It could potentially allow doctors to address some of the most challenging medical programs, help patients understand more about their treatment plan and disease, and educate future physicians.

According to a press release, MediSolutions, a medical device company, hopes to use virtual reality to change how patients are educated in their newest virtual reality platform, MediVRx. The product is said to provide virtual reality educational programming of 3D reconstruction of the human body at a molecular level on topics like Type 2 Diabetes and Atrial Fibrillation.

The press release further notes that virtual reality studies “show that the retention of information delivered via VR is much higher than traditional videos” in a way that patients “won’t just see information – they’ll feel it.” MediVRx is set to be launched in March of 2018.

MediSolutions indicates in the press release that they plan to use virtual reality to give patients a better understanding of their diagnoses and treatments as well as a memorable experience to encourage patient adherence to treatment plans. Neil Keene, the president of MediSolutions explained a company press release:

“Imagine a patient diagnosed with cancer, seeing firsthand how their body functions from the inside out, learning the way in which cancer is infiltrating their internal system and organs, and how a proposed medication can directly influence and correct the prognosis.”

MediSolutions’ system is just one example of the ways virtual reality is being used in the healthcare field.

Virtual reality is also being used to educate medical students. Earlier this year, according to an article in the Guardian, surgeon Shafi Ahmed live-streamed his operation using virtual reality. The article notes that students were allowed to access the camera, observe the surgery, and ask questions which Dr. Ahmed answered while he carried out the surgery.

Students can not only observe from the doctor’s perspective, but can also experience the patient’s perspective. According to an article online, one lab has created a program, “We Are Alfred,” to experience a hypothetical patient’s life – specifically, a 74 year old man named Alfred. Participants use a virtual reality headset, headphones, and hand tracking devices and are fully immersed into Alfred’s story. Participants see and hear as Alfred would, including hearing loss and macular degeneration. This program is said to connect patients and doctors in ways they haven’t before, taking “put yourself in someone else’s shoes” to a new level – a virtual reality level.

Platforms can go further than immersive observations of patient and doctor perspectives to allow students to practice operations in a virtual setting. Programs like ImmersiveTouch are said to be able to replicate surgical touch and feel of specific medical devices.

Beyond education, virtual reality technology is being used to directly treat patients. Some programs are being designed to directly treat conditions. As one example, according to a Forbes article, UbiSoft is introducing a game called Dig Rush to treat children with amblyopia.

 

Diabetes Monitoring Technology Moving Toward Consumer Convenience

The FDA recently approved Abott’s FreeStyle Libre Flash Glucose Monitoring System.  According to Bloomberg, this device marks the first continuous glucose monitoring system that adults can use that does not use diagnosis via taking fingertip blood samples using a fingerstick.

Traditionally, fingersticks required one to prick their finger to obtain blood droplets for diabetes monitoring devices to work.  The Libre flash instead uses a more discreet method of operation–a small sensor wire is inserted below the skin’s surface which continuously measures and monitors glucose levels.  According to Abbott, a mobile reader is used to measure glucose levels when a user waves the mobile reader above the sensor wire.  It is intended for use in people 18 years of age and older with type I or II diabetes.  After an initial 12-hour acclimation period, it can be worn for up to 14 days.  Because a diabetic patient’s pancreas can not produce insulin, those patients frequently must monitor their blood sugar and regularly inject themselves with insulin when their blood sugars spike.

Bloomberg and Reuters report that other companies have been left behind.  Johnson & Johnson is closing its insulin-pump unit after failing to keep up with Medtronic Plc. DexCom Inc., the current leader in glucose-monitoring systems, which, in turn, lost a third of its market value on Sept. 28 after Abbott’s Libre got approval.

The Centers for Disease Control and Prevention notes that more than 30 million people in the U.S. have diabetes.  People with diabetes either do not make enough insulin (type 1 diabetes) or cannot use insulin properly (type 2 diabetes).  When the body doesn’t have enough insulin or cannot use it effectively, sugar builds up in the blood.  High blood sugar levels can lead to heart disease; stroke; blindness; kidney failure; and amputation of toes, feet or legs.

According to Bloomberg, “the bulk of the sales are to the 1.25 million American diabetes patients with the most severe form of the disease, type 1.  There’s a larger, mostly untapped market: the about 20 million Americans with type 2, whose body’s ability to use insulin fades slowly over time and who don’t regularly use tools to manage their disease.”

 

 

FDA Clears First Apple Watch Medical Device Accessory

The FDA recently cleared the first medical device accessory for the Apple Watch — AliveCor’s KardiaBand.  According to AliveCor, the Kardiaband is a mobile, real-time electrocardiogram (EKG) reader that can record an EKG within 30 seconds and display the results on the Apple Watch or iPhone.  In conjunction with the KardiaBand, AliveCor is introducing “SmartRhythm, a new feature within the Kardia app for the Apple Watch.”  AliveCor

Portable EKG readers for smart phones are not new; several are on the market already.  However, none of them can tell the patient when to take an EKG.  The KardiaBand solves that problem.  The combination of the KardiaBand and SmartRhythm will use the Apple Watch’s sensors “to continuously evaluate the correlation between heart activity and physical activity,” and alert the user to take an EKG using the KardiaBand when the “heart rate and activity are out of sync.”  According to Dr. Eric Topol, director of the Scripps Translational Science Institute,

[The KardiaBand] is continuously monitoring your heart rate to let you know if something is potentially off track.  That’s the big difference.

AliveCor eplains that the Kardia app will display the results of the EKG on the Apple Watch and alert the patient if atrial fibrillation (Afib) is detected.  If necessary, the results of the EKG can be emailed directly to a physician.  Dr. Topol believes that this technology will “markedly increase the number of EKGs taken,” which will potentially save lives, because Afib often goes undetected.

The news of KardiaBand’s approval comes within days of Apple’s announcement of the Apple Heart Study in conjunction with Stanford Medicine, which will investigate the detection of Afib using the sensors already embedded in the Apple Watch.  However, in a recent interview, AliveCor’s CEO, Vic Gundotra, distinguished the KardiaBand from the heart rate and activity sensors already found on the Apple Watch:

Apple might be able to say ‘oh your heart rate is high’ …but what does that mean? Does that mean you should go to the hospital? And if you go to the hospital what are they going to do?. Any doctor will say ‘ok come in, let’s get an EKG reading.’ . . . It’s not possible to diagnose atrial fibrillation without FDA clearance. That is a big, big play.

AliveCor touts the FDA’s approval of KardiaBand as a reason patient’s can be confident in the results of AliveCor’s mobile real-time EKG technology.  In another interview, Mr. Gundotra stated

The average consumer doesn’t know what a normal sinus rhythm looks like or what atrial fibrillation looks like. Yet the FDA has cleared our individual algorithms.  The consumer can have confidence that this is FDA-cleared. And frankly, we have the clinical studies to prove it.

The results of a recent study showed a 4-fold increase in Afib detection when using AliveCor’s mobile 30-second EKG technology.  That same study showed that when using mobile EKG technology, such as the KardiaBand or AliveCor’s other device, fewer cases of Afib went undiagnosed.

The KardiaBand is available on AliveCor’s website for $199.

 

FDA Provides Guidance on 3D-Printed Medical Device Products

The U.S. Food and Drug Administration released finalized guidance regarding 3D printing in medical devices.  The guidance document, which issued on December 5, 2017, is based on the FDA’s review of more than 100 devices currently on the market that are manufactured using 3D printers.  Importantly, many of these devices can be tailored to fit a specific patient’s anatomy.  For example, the FDA has reviewed 3D-printed knee replacements and implants for facial reconstruction.

The new guidance gives the FDA’s recommendations regarding the content of FDA submissions, device testing, and manufacturing considerations for 3D printed devices.

In a press release announcing the new guidance, FDA Commissioner Scott Gottlieb stated:

[This guidance] will help manufacturers bring their innovations to market more efficiently by providing a transparent process for future submissions and making sure our regulatory approach is properly tailored to the unique opportunities and challenges posed by this promising new technology.

The new guidance comes on the heels of recent FDA approvals for several 3D-printed devices, including Medicrea’s 3D-printed titanium interbody device for spinal surgery.  The FDA also recently approved a 3D-printed drug tablet, the epilepsy drug Spritam, marketed by Aprecia Pharmaceuticals.

Commissioner Gottlieb further opined that “3D printing is certain to alter the daily practice of medicine where patients will be treated with medical products manufactured specifically for them.”  He noted that 3D printing could one day be used to treat burn patients by printing their own skin cells onto their wounds or used to grow replacement organs.

Commissioner Gottlieb noted, however, that the FDA’s new guidance is intended only “to provide the FDA’s initial thoughts on an emerging technology” and that the FDA’s recommendations likely will change as 3D-printing technology develops.

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