Understanding of Medical Device in Clinical Trail

Understanding of Medical Device in Clinical Trail.

Medical Device.

Regulations. CDSCO Medical Devices Rules, GSR 78 (E) 31st January, 2017 Classification of medical devices and in vitro diagnostic medical devices under the provisions of the Medical Devices Rules, 2017 Classification of newly notified Medical Devices 15 May 2019 MoHFW S.O. 648(E) NOTIFICATION 11 Feb 20 G.S.R. 102 (E) Medical Devices (Amendment) Rules, 11 Feb 2020 Classification of Medical Devices pertaining to paediatric and neonatology 23 Aug 21.

Medical Device India: Definition. According to the Ministry of Health and Family Welfare's notification on February 11, 2020, the definition of medical devices in India has been established, effective from April 1, 2020. The notification covers a wide range of devices intended for use in humans or animals as drugs Medical devices include instruments, apparatus, appliances, implants, materials, or other articles. These can be used alone or in combination and may include software or accessories. The key criterion is that these devices are intended by their manufacturers specifically for use in human beings or animals.

A distinctive feature of these medical devices is that they do not achieve their primary intended action through pharmacological, immunological, or metabolic means Instead, they may assist in their intended function through these means. The purposes of these devices are diverse and include: Diagnosis, prevention, monitoring, treatment, or alleviation of any disease or disorder Diagnosis, monitoring, treatment, alleviation, or assistance for any injury or disability Investigation, replacement, modification, or support of the anatomy or of a physiological process Supporting or sustaining life Disinfection of medical devices Control of conception.

Difference between Device and Drug. Category Medical Devices Drugs Use In-vivo, ex-vivo, in-vitro In-vivo Function Diagnostic, therapeutic, supportive Therapeutic Mechanism of Action Physical interaction with the body Pharmacological, immunological, metabolic Effectiveness Generally independent of user skill Dependent on correct dosage and administration Development Duration Short (months to years), incremental innovation Extensive (decades), large-step innovation Approval Focus Safety and performance Safety and efficacy Clinical Trials Pilot (10-30 patients), pivotal (150-300 patients), post-approval long-term Phase I (20-100 volunteers/patients), Phase II (several hundred), Phase III (thousands), Phase IV (long-term PMS).

Category Medical Devices Drugs Trial Design Placebo/double-blind not possible, depends on risk stratification Placebo/double-blind essential Engineering Involvement Mechanical, electrical, materials engineering Pharmacology, chemistry, biotechnology, genetic engineering Primary Action Not dependent on pharmacological means Requires absorption into the body Lifecycle Short to medium term Long-term.

Classification of Device. 1) Therapeutic: - Invasive / non-invasive - Transient/ short term/long term 2) Diagnostic: - Active - In vitro medical diagnosis.

Classification Rules for Medical Devices. Intended Purpose The primary function and intended use of the device in healthcare settings Time Duration The duration for which the device is intended to be used, categorized into transient, short-term, and long-term Invasiveness Whether the device is invasive (penetrates the body) or non-invasive (does not penetrate the body) Critical Anatomical Locations The specific anatomical areas where the device is intended to be used Active Medical Devices Devices that require external power or another energy source to function effectively These factors help regulatory bodies and healthcare providers appropriately classify and assess the safety and efficacy of medical devices for their intended applications.

Medical Device Rules 2017 Classification. In India, medical devices are classified based on their potential risks to patients and users The classification ranges from Class A to Class D, which correlates with the level of risk associated with the device Class A Low risk Class B Low moderate risk Class C Moderate high risk Class D High risk.

Indian Rules: Types of Devices. Medical devices in India are categorized into several groups based on their use and interaction with the human body These include non-invasive devices for external contact with the skin, devices for channeling or storing substances, and devices that modify the composition of substances Additionally, there are invasive devices that enter body orifices, including those used for transient, short-term, and long-term durations Devices connected to active medical devices and those used for sterilization or disinfection also fall under specific categories.

Specialized Categories of Medical Devices. Certain medical devices in India fall into specialized categories based on their functionality. These include: In Vitro Diagnostic Medical Devices (IVMD): Used for detecting transmissible agents, blood grouping, tissue typing, self-testing, and near-patient testing Active Therapeutic Medical Devices: Used for administering or exchanging energy Devices Incorporating Medicinal Products or Biological Materials: Including those with animal or human cells, tissues, or derivatives Devices for Sterilization or Disinfection: Specifically designed for these purposes in medical settings Contraceptive Devices: Devices designed for contraceptive use also fall under a distinct category.

Device Data Requirements.

Regulatory Requirements. In India, medical devices must meet stringent regulatory standards to ensure safety and efficacy. Compliance involves: Clinical Evidence: Gathering data through trials to validate safety and performance Technical Documentation: Detailed specifications and manufacturing processes documentation Product Testing: Rigorous testing to confirm adherence to regulatory and performance standards Manufacturing Quality: Adherence to Good Manufacturing Practices (GMP) and robust Quality Management Systems (QMS) to maintain consistency and reliability These requirements ensure that medical devices in India meet high standards of quality, safety, and effectiveness.

Investigational Medical Devices. An investigational medical device in India refers to a device that: Does not have a predicate device: This means it does not have a similar device already approved for use Is licensed under specific rules: Such as rules allowing new intended uses, new populations, new materials, or major design changes Undergoes clinical investigation: It is being evaluated in clinical studies to assess its safety, performance, or effectiveness Investigational medical devices are subjected to rigorous evaluation to ensure they meet regulatory standards before potential approval for broader medical use.

Predicted Devices. In India, a predicate device refers to: First-time approval: It is the first device of its kind to be approved for manufacture or import by the Central Licensing Authority Similarities in intended use, materials, and design: It shares the same intended use, materials of construction, and design characteristics as the device proposed for licensing in India Predicate devices serve as benchmarks for new devices seeking approval, ensuring they meet established standards of safety and performance before being licensed for use in India.

Clinical Evidence. Clinical evidence in India is defined as: For in vitro diagnostic medical devices: It includes all information derived from specimens collected from humans. This data supports the scientific validity and performance of the device for its intended use For medical devices: It comprises clinical data and a clinical evaluation report. These documents provide evidence supporting the scientific validity and performance of the device for its intended use Clinical evidence is essential in demonstrating that medical devices and in vitro diagnostic devices are safe, effective, and suitable for their intended medical purposes according to regulatory standards in India.

Clinical Investigation. In India, a clinical investigation refers to: Systematic study: It involves a structured and methodical examination of an investigational medical device Involves human participants: The study is conducted using human participants Objective: The primary aim is to assess the safety, performance, or effectiveness of the investigational medical device Clinical investigations are crucial steps in evaluating new medical devices, ensuring they meet regulatory standards for safety and performance before potential approval and broader use in healthcare settings.

Clinical Data. Clinical data in India refers to: Safety and performance information: It encompasses data obtained from the clinical use of a medical device Sources of clinical data include: Clinical investigations: Studies specifically conducted to assess the device in question Literature reviews: Studies or investigations reported in scientific literature, demonstrating equivalence to the device being evaluated Clinical experience: Both published and unpublished reports on the device itself or similar devices, where equivalence to the device in question can be established.

Pilot Clinical Investigation in India. Pilot clinical investigations in India are essential early-stage studies for medical devices. These investigations start with exploratory studies on a small group of patients with the specific disease or condition. These initial studies provide insights into the device's performance and safety but are not designed to offer definitive evidence for specific therapeutic claims Initial Human Studies: These studies are conducted for the first time on human participants to collect preliminary safety and performance data As the investigation progresses, definitive studies are performed on a larger patient population. These studies aim to gather comprehensive evidence to evaluate the device's safety and effectiveness for its intended use. They confirm the device's effectiveness and help identify any potential adverse effects For investigational devices without a predicate, pivotal studies are needed to gather safety and effectiveness data for Indian patients, except for Class A devices. The Central Licensing Authority may also require pilot study data to ensure it matches data from outside the country.

Pilot Clinical Investigation: Objective. Assess Feasibility: Determine the practicality of the device in real-world settings Explore Eligibility Criteria: Test and refine criteria for participant selection in pivotal studies Ascertain Potential Harm: Identify any possible risks or adverse effects associated with the device Study Device Mechanism: Understand how the device works and its impact on the body Validate Outcome Measures: Confirm the methods used to measure the device's effectiveness Validate Surrogate Outcomes: Use defined mechanisms to establish surrogate markers for outcomes Evaluate Logistics: Assess the practical aspects of conducting a large-scale pivotal investigation.

Pilot Clinical Investigation: Examples. Migraine Treatment Device: Study Type: Randomized Double-Blind Comparison: Use Device vs. Sham Device Outcome Measure: Change in Pain Visual Analogue Scale (VAS) Hair Removal Device: Study Type: Safety and Effectiveness Outcome Measure: Proportion of subjects with at least 30% hair reduction from baseline HCV RNA Testing: Study Type: Evaluation of Dried Blood Spot Outcome Measure: Sensitivity and specificity of assays for HCV RNA detection compared to Abbott Real-time HCV.

Clinical Investigation Requirements.

Investigational Medical Device- Clinical Investigation Requirements Table 1 Design analysis data. Table 2 Biocompatibility and Animal Performance Study. Table 3 Information specified Table 4 Investigator's Brochure Table 5 Clinical Investigational Plan Table 6 Case Report Form Table 7 Serious adverse event form Table 8 Informed Consent Form Table 9 investigator's undertaking Ethics Committee approval, if available Regulatory status in other countries Proposed Instructions for use and labels.

Table 3 Design Analysis data The agreement between the Sponsor and Principal and coordinating investigator(s) Appropriate insurance certificate, if any Forms for reporting any adverse event and serious adverse event Report of biocompatibility tests along with rationale for selecting these tests including a summary report and conclusion of the study Results of the risk analysis Animal Performance study data Clinical Investigational Plan Pilot and Pivotal Clinical Investigation data including that, if any, carried out in other countries.

Table 5 Clinical Investigation Plan 1.1 General 1.1.1 Introduction 1.1.2 Identification of the clinical investigation plan 1.1.3 Sponsor 1.1.4 Principal investigator, coordinating investigator and investigation site 1.1.5 Overall synopsis of the clinical investigation 1.2 Identification and description of the investigational medical device (a) Summary description of the investigational medical device and its intended purpose (b) Details concerning the manufacturer of the investigational medical device.

(c) Name or number of the model or type, including software version and accessories, if any, to permit full, identification (d) Description as to how traceability shall be achieved during and after clinical investigation, for example by assignment of lot numbers, batch numbers or serial numbers (e) Intended purpose of the investigational medical device in the proposed clinical investigation (f) The populations and indications for which the investigational medical device is intended (g) Description of investigational medical device including any materials that will be in contact with tissues or body fluids (h) Summary of the necessary training and experience needed to use the investigational medical device (i) Description of the specific medical or surgical procedures involved in the use of investigational medical device.

1.3 Justification for the design of the clinical investigation 1.4 Risks and benefits of the investigational medical device and clinical investigation 1.5 Objectives and hypotheses of the clinical investigation 1.6 Design of the clinical investigation 1.6.1 General 1.6.2 Investigational medical device and comparator 1.6.3 Subjects 1.6.4 Procedures 1.6.5 Monitoring plan 1.7 Statistical considerations 1.8 Data management 1.9 Amendments to the Clinical investigation plan.

1.10 Deviations from clinical investigation plan 1.11 Device accountability 1.12 Statements of compliance 1.13 Informed consent process 1.14 Adverse events, adverse device effects and device deficiencies (a) Definitions of adverse events and adverse device effects (b) Definition of device deficiencies (c) Definitions of serious adverse events and serious adverse device effects and, where appropriate, unanticipated serious adverse device effects (d) Time period in which the principal investigator shall report all adverse events and device deficiencies to the sponsor and, where appropriate, to Ethics Committee and the regulatory authority (e) Details of the process for reporting adverse events (date of the adverse event, treatment, resolution, assessment of both the seriousness and the relationship to the investigational medical device).

(f) Details of the process for reporting device deficiencies. (g) List of foreseeable adverse events and anticipated adverse device effects, together with their likely incidence, mitigation or treatment. (h) Emergency contact details for reporting serious adverse events and serious adverse device effects 1.15 Vulnerable population 1.16 Suspension or premature termination of the clinical investigation 1.17 Publication policy.

In Vitro Diagnostic Medical Device. A "new in vitro diagnostic medical device" refers to any medical device used for in vitro diagnosis that has not yet been approved for manufacture or import by the Central Licensing Authority. It is tested to confirm its performance for the relevant analyte or parameter, including necessary technology and procedures.

New In Vitro Diagnostic Medical Device Approval from registered ethics committee Source and quantity of samples which shall be used during evaluation; Device description including specification of raw material and finished product, data allowing identification of the device in question, proposed instruction for use, labels and regulatory status in other countries, if any; In house performance evaluation data used to establish stability, specificity, sensitivity, repeatability and reproducibility; Clinical performance evaluation plan stating in particular the purpose, scientific, technical or medical grounds and scope of evaluation Case report form Undertaking by investigators List of laboratories or other institutions The scheduled duration for evaluation and, in case of devices for self- testing, the location and number of lay persons involved;.

An undertaking that the device in question conforms to the requirements of these rules, apart from aspects covered by evaluation and apart from those specifically itemized in the undertaking, and that every precaution has been taken to protect the health and safety of the patient, user and other persons Performance evaluation report from a laboratory designated under sub- rule (1) of rule 19.

Post Marketing Clinical Investigation. This involves activities beyond surveillance conducted after a medical device has received marketing approval for its intended indication The CLA may require these investigations to optimize the device's intended use These studies include additional drug-device interaction assessments, safety evaluations, and investigations to support use under the approved indication.

Clinical Evaluation of Medical Devices. A methodologically rigorous, ongoing process designed to: Collect, assess, and analyze clinical data systematically, ensuring that the data is robust, accurate, and relevant to the device's intended use Evaluate sufficient clinical evidence to confirm that the medical device meets all essential safety and performance requirements, thereby ensuring its effectiveness and reliability for patients.