Neuroprosthetics

Prof: Lisa CrockettPresenters: Veronica Dasari Srivani Pabbaraju Vrushank Shah Swathi Kiran S Muhammad Tayyab

Neurological Disorders• It is expected that there are more than 600 Neurological disorders that are

associated with brain, spine and the nerves that connect them. • A dysfunction/malfunction in any part of the nervous system may lead to

neurological disorders with associated symptoms like trouble moving, speaking, swallowing, breathing, or learning, problems with memory, senses, or mood.

• Treatments for these neurological disorders can range from medications, device-based therapies (such as deep brain stimulation), surgeries (such as procedures to remove tumors, retracting blood clots), physical therapy, stem cell therapy and rehabilitation.

• There are some neurological disorders which require the use of artificial prosthesis which either acts as a replacement for any missing functional part of the body or as a support for the functional part of the body

Neuroprosthetics• Imagine a single day where a functional part of body is partially or

completely not functioning and where you fail to hear, see, speak, move. But there are millions of people who are living a compromised life and thanks to today’s science which has brought light to those individuals in the form of Neuroprosthetics.

Definition:• Neuroprosthetics are devices implanted in the body that simulate the

function of an organ or organ system that has since failed due to disease or injury

Functions:• It functions by enabling an individual to see, hear, feel sensory stimuli,

perform motor based activities and restoring damaged cells and also by acting as a replacement for any functional part.

Working Principle

Types of NeuroprostheticsThere are three main types of Neuroprosthetics:A)Sensory Neuroprosthetics: (Input neural interfaces) Get information into sensory areas like hearing and sight.An external device captures sensory information no longer obtainable by biological means, converts it into a series of electrical signals interpretable by the brain and sends them to the implant, which in turn passes the information to the brain. Ex: Cochlear implants, visual prosthetics

Image : Cochlear Implants

Restoring Sight with Microchips

Types of NeuroprostheticsB) Motor Neuroprosthetics: (output neural interfaces)Motor Neuroprostheses are a type of brain-machine interface (BMI) that seek to extract

signals from the central or peripheral nervous system and deliver them to control devices.

Assist in regulation or stimulation of motor functions with issues, such as using the arm and hand to pick up an object.

Types of Neuroprosthetics

C) Cognitive prosthetics:

•Cognitive prostheses seek to restore cognitive function to individuals

with brain tissue loss due to injury, disease, or stroke by performing the

function of the damaged tissue with integrated circuits

•Used in treatment of Alzheimer's, Parkinson's, epilepsy and

depression.

Target Population• The primary target population for Neuroprosthetic devices is individuals suffering from

sensory or motor disabilities . Neuroprosthetics can also enhance the existing skill hence the normal individuals can be considered as secondary target population

Safety and Efficacy• Given that Neuroprosthetics is still in research phase there are a number of research

studies that have excelled in making working prototypes for hands or limbs.• As there are limited number of approved Neuroprosthetics, the safety and efficacy cam

only be proved by success of the ongoing studies. E.g. In a research study at University of Washington, successfully demonstrated direct artificial connection from region of brain associated with movement of limb in monkeys whose limbs were temporarily anesthetized. This shows that Neuroprosthetics may help individuals suffering from paralysis regain control over their body.

• Similarly, in a visual implant study at the University of Tübingen conducted on 22 patients who were either completely blind or had minimal vision showed that they regained some amount of vision.

• Caltech has successfully implanted an individual suffering from quadriplegia which enabled him to perform gestures and also they quoted that he could even play “rock, paper, and scissors”.

• These studies can confirm that the developing Neuroprosthetics are safe and efficacious

Adverse Events• The main adverse event in the case of Neuroprosthetics is the risk of surgery. Any

implant in the brain causes a major risk for infections and the surgery itself is very complicated.

• In the case of individuals suffering from Parkinson’s disease and treated with Deep Brain Stimulations(DBS) were found to have hypomania, personality disorders, psychiatric disorders, and higher suicide rate.

• Besides the risks associated with the brain surgery and risks of infections, many studies conducted have showed results without any adverse events.

Non-clinical ConsiderationsEvaluating Neuroprosthetics •Non-clinical device testing is important to mitigate risk and to support potential clinical studies or market approval. In addition to standard device testing such as biocompatibility, sterility, and electrical safety, Neuroprosthetics may have unique testing considerations, for example: •Neuroprosthetics may measure signals from the neurons; so important factors to consider include electrode reliability, signal-to-noise ratio, artifact removal (e.g., eye or muscle movement), and battery longevity. • The signal of interest may vary among and within subjects over time, making the quality of Neuroprosthetics input signal for a specific individual at a specific time very difficult to predict. • If the device provides stimulation to the nervous system, determining maximum safe levels of stimulation that can be applied to neurons is important. 

Non-Clinical Considerations

Challenges: •What are the key areas of non-clinical testing that should be addressed for Neuroprosthetics technologies? For example, what test methods and metrics should be presented to demonstrate long-tern reliability of implanted electrodes in the central or peripheral nervous systems? Can new methods/metrics be developed to more accurately assess the long term reliability? •When should animal studies be performed prior to implantation into humans (e.g., to determine device reliability or stimulation safety) and what general study design principles (and results) should be examined to determine whether preclinical data supports moving to human study?

Clinical ConsiderationsNeuroprosthetics have the potential to benefit people with severe disabilities by increasing their ability to interact with their environment. Implantation carries potential risks such as neural tissue damage that can result in additional functional or sensory deterioration. The development of adequate clinical study designs for Neuroprosthetics designs that are intended to support marketing authorization in the U.S. is essential to the successful translation of Neuroprosthetics from concept to patient access.

Challenges•Can different disease states or conditions such as patients with SCI and patients with amputations be served by the same Neuroprosthetics technology?•How should one consider the level of functional loss in designing Neuroprosthetics technologies versus targeting particular diseases or conditions?  

Clinical Considerations• Comorbid conditions, such as phantom limb pain, post-traumatic stress disorder,

depression, cognitive disability, and loss of sensation may occur within specific patient populations and may affect acceptance and successful integration of Neuroprosthetics technologies. How these considerations should be incorporated into clinical studies and what clinical metrics exist to measure these phenomena?

• What are important activities of daily living and quality of life factors to measure in a clinical study for various populations? What are important patient-oriented clinical metrics for daily living and quality of life? And what patient-oriented metrics are available to assess the risk tolerance of the device as well as the added benefit over a state-of-the-art device?

• What individual subjects consider most important for their quality of life may not only vary between patient populations, but also between individuals. How should this be assessed in clinical studies?

Market Scope• According to a new report by Allied Market Research titled, "Global

Neuroprosthetics Market (- Size, Share, Global Trends, Company Profiles, Demand, Insights, Analysis, Research, Report, Opportunities, Segmentation and Forecast, 2013 - 2020", the global Neuroprosthetics market is expected to reach $14 billion by 2020, registering a CAGR of 15.8% from 2014 to 2020.

North America Neuroprosthetics Market, By Type, 2014 - 2024 (USD Million)

Regulatory Pathway• Regulatory Pathway of each Neuroprosthetics is different from the other. Some has

even be approved for HDE status such as “Argus II Retinal Prosthesis System”• Most of the Neuroprosthetics are approved under Class III PMA or De-Novo pathway.

After De-Novo Pathway, devices are reclassified under Class III PMA or Class II depending upon the risks associated with the Neuroprosthetics.

Examples: • Cochlear Implants from Sensory Neuroprosthetics:

Nucleus® Hybrid™ L24 Cochlear Implant System was approved under PMA P130016.

• Argus II Retinal Prosthesis System was approved for HDE under HDE No. H110002. 1. Motor Neuroprosthetics:

Neurocontrol freehand system was a Surgically implanted Neuroprosthetics, approved under the PMA No. P950035 due to the clinial considerations associated with this device. Ever since the approval of this device, there has been 10 supplements for different reasons such as Process Change, Labelling Change and Location Change.

Regulatory PathwayDeka Arm System was first approved under the De-Novo Classification, however, the FDA approved the request to reclassified this device under class II.

Some of the Useful FDA Guidance Document Links For PMA Application•http://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/premarketapprovalpma/

•https://www.gpo.gov/fdsys/pkg/USCODE-2010-title21/html/USCODE-2010-title21-chap9-subchapV-partA-sec360e.htm

•http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketApprovalPMA/ucm143067.htm

Current Regulatory Challenges • FDA is still looking for the proper regulatory pathway which can be used to ensure

that the BCI (brain computer Interfaces) are safe. • No clear guidelines available• Each class of Neuroprosthetics has different risks, so, the regulations clearly vary

from one device to another. For example: Implants are called the riskiest devices which are inserted in the body after brain surgery, so, they are inserted under controlled laboratory settings.

• Unavailability of the ICH Guidelines• Unavailability of the Neurological tissue contact tests in any guidance documents

Suggestions to Overcome these Challenges

• Leniency in the regulations to promote more research and development in the BCI field.

• Providing the Clearance guidelines, even from the Engineering Phase• Strong Collaboration with the EU and JAPAN to develop ICH Guidelines for

Neuroprosthetics• Proper Communication between the FDA, researchers and manufacturers may lead

to create some proper guidelines which can help to speed up the regulatory process.

References• Anissimov, M., & Harris, B. (n.d.). Retrieved December 06, 2016, from

http://www.wisegeek.com/what-are-neuroprosthetics.htm• Neuroprosthetics. Retrieved December 06, 2016, from

http://creationwiki.org/Neuroprosthetics • Treatments for Neurological Disorders - The Mount Sinai Hospital. (2016). The Mount

Sinai Hospital. Retrieved 8 December 2016, from https://www.mountsinai.org/patient-care/service-areas/neurology/treatment

• Pancrazio, J. & Peckham, P. (2009). Neuroprosthetic devices: how far are we from recovering movement in paralyzed patients?. Expert Review Of Neurotherapeutics, 9(4), 427-430. doi:10.1586/ern.09.12 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685465/

• Stingl, K., Bach, M., Bartz-Schmidt, K., Braun, A., Bruckmann, A., & Gekeler, F. et al. (2012). Safety and efficacy of subretinal visual implants in humans: methodological aspects. Clinical And Experimental Optometry, 96(1), 4-13. doi:10.1111/j.1444-0938.2012.00816.x http://onlinelibrary.wiley.com/doi/10.1111/j.1444-0938.2012.00816.x/full

• Brain implants and cognitive side-effect trading. (2009). Mind Hacks. Retrieved 8 December 2016, from https://mindhacks.com/2009/02/26/brain-implants-and-cognitive-side-effect-trading/

Ref – Contd.• prnews.com: News releases: Article on Global Neuroprosthetics Market, Retrieved on

DEC 6, 2016. http://www.prnewswire.com/news-releases/global-neuroprosthetics-market-is-expected-to-reach-14-billion-by-2020---allied-market-research-283818951.html 

• www.ncbi.com: Books on Medical devices: Neuroprosthetics, Retrieved 6 December 2016 https://www.ncbi.nlm.nih.gov/books/NBK3897/?report=printable

• Neuroprosthetics. (2016). Fraunhofer Institute for Biomedical Engineering. Retrieved 6 December 2016, from https://www.ibmt.fraunhofer.de/en/ibmt-core-competences/ibmt-biomedical-engineering/ibmt-medical-engineering-neuroprostetics/ibmt-medical-engineering-neuroprosthetics.html

• Premarket Approval (PMA). (2016). Accessdata.fda.gov. Retrieved 8 December 2016, from http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P950035S004

• What is a Cochlear Implant?. (2016). Fda.gov. Retrieved 8 December 2016, from http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/CochlearImplants/ucm062823.htm

• (2016). Fda.gov. Retrieved 8 December 2016, from http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/EarNoseandThroatDevicesPanel/UCM443996.pdf

Neuroprosthetics

Team 3