Regulatory Insights into Neurological Devices and Neurovascular Stent for Brain Aneurysm

Neurology is concerned with diagnosing and treating neurological diseases and disorders affecting the brain and spinal cord. Numerous neurological disorders and conditions, such as Alzheimer's disease, Parkinson's disease, major depression, epilepsy, spinal cord injury, and brain damage, can now be diagnosed, prevented, and treated with the aid of neurological devices that can enhance function and restore hearing and vision. Neurovascular stents are an emerging treatment option for brain aneurysms that offer several advantages over traditional treatments. This article describes the most recent regulatory framework for neurological devices in the United States and the regulatory requirements for marketing clearance of neurological devices in the United States. The Centre for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA) regulates neurological devices .

• Many neurology-related items are advancing in clinical trials in the United States, where neurology research and development are accelerating.

II. History of Neurological Medical Devices
• Stephen Hales and Robert Whytt were the first to study animal neuron function scientifically in the eighteenth century. Traumatic brain damage produces aphasia, seizures, and movement problems. Jean-Martin Charcot and William Gowers classified nerve system disorders. Targeted electrical stimulation to map brain function began in the 19th century. In addition to these contributions, animal research and microscopic inspection of nerve cells underpin our brain and nervous system expertise. • Hans Berger devised the electroencephalograph (EEG) in the 1920s to record brain activity.
Neurologists can now make more accurate diagnoses and provide more specific treatments and rehabilitation thanks to the EEG, lumbar puncture, and cerebral angiography. In the early 1970s and 1980s, computerized axial tomography (CT) scanning and magnetic resonance imaging (MRI) provided detailed, noninvasive pictures of the brain's interior, making brain illnesses easier to diagnose and treat. Cerebral imaging. Many medications for neurological disorders like Parkinson's disease, multiple sclerosis, and epilepsy have been developed since the discovery of chemical agents in the central nervous system and their roles in transmitting and blocking nerve impulses. CT scanning and other more precise methods for identifying lesions and other neural tissue anomalies have also helped neurosurgery.

III. Classification of Neurological Medical Devices
A) Types of Neurological Devices, depending on the level of risk, medical devices are divided into one of three classifications: Class I neurological devices are not common. Class II or class III devices are the most common classifications for neurological devices. B) Types of Neurological Devices Based on Usage a) Neurodiagnostic Devices: These involve the investigation and recording of electrical activity in the brain, CNS and PNS. Observing the electrical signals of these nervous systems provides vital information that can assist in the diagnosis and treatment of a number of neurological conditions. Conditions include epilepsy, headaches, head and spinal traumas, seizures, sleep disturbances, strokes, and unexplained comas. Examples of Neurodiagnostic Devices: Electroencephalography, long-term monitoring, intraoperative neuromonitoring, polysomnography, evoked potential studies and nerve conduction studies are the most common procedures performed by neurodiagnostic technicians. b) Neurostimulation Devices: Neurostimulation technologies provide relief to an increasing number of individuals with chronic neurologic and mental disorders. Neurostimulation therapies employ both invasive and noninvasive electrical stimulation of brain circuits to control neural function. This article explores established invasive electrical stimulation techniques used clinically to induce neuromodulation

IV. Regulatory Process
• Regulatory requirements for an experimental agent may be affected by considerations that are productspecific. • During the pre-IND conference, where these subjects should be carefully discussed with the FDA, the IND sponsor should offer pertinent preclinical data, manufacturing information, and animal safety tests to support the intended clinical development route. • The agency's engagement can help define the eventual growth strategy and recommend the kind of follow-up research that is pertinent to a particular agent. • The development of a product will be aided by scheduling interactions with regulatory organizations at regular intervals. • Regulatory agency standards tighten when a Neurological Medical device product moves through the trials and license processes from the first to the second the third phases. • A sponsor should be able to evaluate the identification, purity, quality, dose, and safety of a Neurological Medical Device product for early-phase clinical research. • A potency assay to evaluate the compatibility of the finished Neurological Medical Device, with applicable lot release parameters, should be established prior to starting the clinical investigations, which are intended to show compelling Safety and level of risk for a marketing application. • To support the licensing of a neurological product, manufacturing procedures and all testing techniques for the product release (21 CFR 882) must be validated. • Sponsors should speak with the FDA's CDRH early on in the development of the Device to address any issues pertaining to a particular product.

V. Regulatory Standards for Neurological Medical Devices
• In order to make the evaluation process rigorous and predictable, the FDA recognizes standards developed by organizations such as the International Organization for Standardization (ISO) and the American Society for Testing and Materials (ASTM) International (ISO). • By selecting the "Neurology" category in the Specialty Task Group Section of the FDA Recognized Consensus Standards database, sponsors can access all of the national and international standards applicable to neurological devices that the FDA has recognized. • Class II devices require additional controls besides traditional controls in order to provide a reasonable assurance of safety and efficacy. • A producer must consistently comply with Section 513(a)(1)(A) of the Federal Food, Drug, and Cosmetic Act (the Act); address the specific health risks listed in Section 513(a)(1)(B) of the FD&C Act by adhering to the recommendations in the guidance or guidelines; or use another method that provides equivalent assurances of safety and efficacy.

VI. Considerations for Pre-Clinical Development of Neurological Medical Device
• In this step, in vitro or in vivo animal testing evaluates the device's toxicity, pharmacological effects, and safety. • Animals undergo acute and chronic tests using the device. Acute investigations usually last one to two days. Chronic studies last three to 365 days. • If the test fails and the animals die, a necropsy determines the device's failure. The animal tissue surrounding the device is removed and sent for pathological investigation. • Failures must be reported to FDA. After the device fails, the client must figure out why and fix it. If the test works, the animal survives, and it's minimally invasive, they'll be used again. • A client can request a necropsy after a successful test to see how the gadget impacts animal tissues.

VII. Considerations for Clinical Development of Neurological Medical Devices
Before evaluating new technologies, lab studies on animal and human cells take years. If early laboratory research is effective, the FDA approves additional laboratory and human trials. Human testing of an experimental technology is permitted. Medical device clinical trials use only patients with the product's intended disease. Drug clinical trials have several pathways. Medical device clinical trials depend on risk and class. Surgical gloves, bandages, and other low-risk devices don't need clinical trials.
Medication trials include a few healthy people. In medical device clinical trials, patients have the product's intended disease. Healthy people should not use it. Surgical implants such as cardiac pacemakers, coronary stents, prosthetic heart valves, etc. may not be tested in healthy people. There are three different stages for medical device clinical studies. They are: 1)Pilot Study: To evaluate the viability, duration, cost, and adverse effects and to improve the study design, a small-scale preparatory investigation known as a "pilot study" is conducted. Another term for an important study is a feasibility study. Pilot studies are often single-centre studies with a small subject population that are intended to achieve any number of goals within a clinical development programme. The study, which aims to assess the preliminary performance and safety of the gadget, entails 10 to 30 participants with the disease or condition. It also provides guidelines for future study design and equipment adjustments.
2)Pivotal Study: Important research is also carried out to show that the gadget is safe and efficient for a particular purpose in a specified patient population. Typically, 150 to 300 people with the illness or condition take part in the trial to evaluate the device's preliminary performance and safety. A critical study's findings are utilized to get regulatory approval to market the gadget. All clinical trial results, additional data pertaining to the device's production, preclinical findings, and administrative data are being submitted to the FDA for review.

3)Post-Approval Study:
This level is similar to Phase IV of clinical drug trials. The objective is to comprehend the device's long-term efficacy and any potential negative effects related to its use. The companies will now assess the device's cost-effectiveness in relation to current technology by comparing it to comparable goods. Even after the technology is made available to the general public, this research still goes on. By learning about medical device clinical and regulatory processes, products can be put on the market to benefit patients or society.

VIII. Considerations for Marketing And Post-Marketing Of Neurological Medical Devices A. Marketing: Submission Type Description Pre-submission
It enables applicants to obtain FDA feedback on future or approaching IDE applications or other premarket submissions, such as the review of automatic class III designations, PMA applications, premarket notice 510(k) and HDE applications. IDE (Investigational Device Exemption) It permits the use of an investigational device in a clinical trial to collect data on its safety and effectiveness. Unless an exemption applies, an Investigational Device Evaluation (IDE) must be approved prior to any clinical evaluation of an investigational device conducted in the United States. HDE (Humanitarian Device Exemption) An HDE is an application used for selling a HUD. An HDE is subject to numerous profits and uses constraints and is expected to prove safety and a likely benefit for the intended patient population.

De novo
Applicants may submit a de novo application to request a class II or class I classification for medical devices that are unique and lack a suitable predicate device. Class II de novoclassified devices can serve as predicates for future 510(k) submissions if they are commercially available.

510(k) Premarket Notification
In terms of intended use, technological characteristics, and performance testing, a 510(k) indicates that the new device is almost identical to a predicate device.

PMA (Pre-Market
Approval) The PMA is the most stringent premarket filing type. The sponsor must provide sufficient assurance that the device is safe and effective for its intended use before the FDA will approve a PMA. 2) Active Surveillance: As part of the Sentinel Program, the FDA is constructing a new national system to identify potential safety concerns. The system will utilize extremely large electronic health databases, such as registries, administrative and insurance claims databases, and electronic health record systems, to continuously monitor the safety of licensed medicinal products. This technology will not replace the FDA's current methods for evaluating post-market safety but will supplement them.

IX. Case Study of Neurological Medical Device
Neurointerventional device: A neurovascular stent Example: DEVICE TRADE NAME: Neuro form Atlas Stent DEVICE GENERIC NAME: Intracranial Coil-Assist System COMPANY: Stryker necked brain aneurysms). A wire is used to insert the self-expanding metal (nitinol) tube-shaped device (stent) known as the Neuroform Atlas Stent System inside a brain artery.

B. Working:
A tiny catheter and delivery wire with the Neuroform Atlas stent is inserted by a doctor through an incision into the femoral artery. To maintain embolization coils put in the sac of the aneurysm in place, the Neuroform Atlas stent is precisely guided to the aneurysm and permanently implanted.

C. Contraindications:
• Possess a parent vessel size outside the range mentioned • Have not taken anti-platelet medications before having a stent implanted • Possess an ongoing bacterial infection • Are not suitable for use with anticoagulant and antiplatelet treatment • Possess an already-existing stent in the parent artery at the intended intracranial aneurysm site.

D. Clinical study:
In the clinical study of 124 patients with posterior circulation wide-necked brain aneurysms treated with the Neuroform Atlas Stent System, 77% of the aneurysms were completely sealed off at one year without the need for re-treatment or significant constriction of the parent artery (stenosis). 18.1% of the patients in the research received treatment for significant adverse effects, such as mortality, stroke, or temporary blood supply obstruction (transient ischemic attack or TIA). E. Regulatory aspects: As the device is high risk comes under class III. To market this device, it requires Premarket Approval To obtain PMA the manufacturer must provide the safety and efficacy data of the device through pre-clinical and clinical studies. The manufacturer must also comply with the quality and safety parameters as per US FDA Regulations. This stent recently got approval on 3 rd June 2020, by FDA through a PMA application having safety and efficacy.