The NMPA granted innovation approvals to MediBeacon Inc.’s transdermal GFR measurement system (TGFR) and issued a review report.
The published review reports like this one serve as important references for you to understand what the regulatory authorities are thinking and evaluating during their review process. We have been following the list for the past several years and review the relevant ones for our clients’ specific products to gain more clarity and be more efficient in their submission and approval process. As NMPA standardizes and streamlines the review process for fast-track approval, domestic and overseas players can benefit from our expertise and experience.
Product overview
- Product structure and composition
- Intended Use
This product is used in combination with our company’s Remapirazine Injection (Lumitrace) to assess the patient’s glomerular filtration rate (GFR). It is suitable for patients with a GFR between 15 ml/min/1.73m² and 120 ml/min/1.73m². It is not suitable for dialysis patients, anuric patients, or patients with rapidly changing renal function, and it is not used for diagnosing acute kidney injury (AKI). This product cannot be used alone for diagnosis and should be comprehensively evaluated by a doctor according to relevant diagnostic and treatment guidelines.
- Model/Specification
- Working principle
The LED light source of the device emits blue light to excite the tracer to produce green light. The device measures the rate of fluorescence clearance of the tracer over time to determine the glomerular filtration rate (GFR).
Pre-clinical
- Product Performance Study
The product’s performance indicators include appearance and structure, light wavelength, average light power, light source power, power stability, linearity of the optical receiver, sensor linear response, signal stability, response time, signal crosstalk, measurement accuracy, battery runtime, software functions, network security, sensor sampling frequency, computing efficiency, clamping force, adhesive strength, over-temperature requirements, electrical safety, and electromagnetic compatibility. The applicant has submitted performance study data and testing reports, all of which meet the product’s technical requirements. - Biocompatibility
Since the product’s sensor makes prolonged contact with human skin, the applicant conducted a biocompatibility evaluation based on GB/T 16886.1-2022, covering cell toxicity, sensitization, and intradermal reactions. The results confirm that the biocompatibility risks are acceptable. - Cleaning and Disinfection
The main unit of the product is reusable and requires cleaning and disinfection. The applicant provided specified cleaning and disinfection methods, along with validation reports demonstrating the effectiveness of these methods. - Product Shelf Life and Packaging
The product has a 5-year operational life, with sensors being single-use only and a shelf life of 2 years. The applicant submitted shelf life studies in compliance with the “Active Medical Device Shelf Life Registration Technical Review Guidelines.” Additionally, packaging stability tests and environmental trials were conducted, confirming that the packaging meets stability requirements. - Software Research
The product includes monitoring software, controller software, and controller firmware, all with high security levels. Based on the “Medical Device Software Registration Review Guidelines (2022 Revision)” and “Medical Device Network Security Registration Review Guidelines (2022 Revision),” the applicant submitted software and network security research reports. Notably, the glomerular filtration rate algorithm is new, and relevant research was provided, confirming that the software development process is standardized, with acceptable residual risks. - Safety
The product meets the following standards:- GB 9706.1-2020: Basic safety and performance requirements for medical electrical equipment
- YY 9706.102-2021: Electromagnetic compatibility standards for medical electrical equipment
- GB/T 20145-2006: Photobiological safety of lamps and lamp systems
The applicant submitted test reports confirming the product complies with these safety standards.
- Other Studies
The applicant designed simulation experiments to verify the device’s measurement accuracy under both healthy and compromised renal conditions. Additionally, safety evaluations were conducted for optical and thermal safety, with results confirming compliance with safety limits. Further verification of the sensor’s mechanical properties, linearity, uniform irradiation, and optical stability was performed, as well as testing of the sensor’s cable tension, bending, and torsional rigidity, all of which met the required performance standards.
Clinical
The applicant conducted clinical trials to evaluate the safety and effectiveness of the percutaneous glomerular filtration rate (GFR) dynamic monitoring system with MB-102 (Remapirazine) fluorescence. Three phases of clinical trials were carried out: Phase I determined the pharmacokinetics of MB-102 when used together with the monitoring system; Phase II verified the consistency between MB-102 plasma GFR and iodixanol plasma GFR; Phase III verified the consistency between the percutaneous MB-102 fluorescence GFR and plasma MB-102 GFR. Phase III served as the primary clinical evidence and was the key study.
- Phase II Clinical Trial:
This trial used a single-group design and enrolled 234 participants. The purpose was to verify the consistency between MB-102 plasma GFR and iodixanol plasma GFR. The primary endpoint was the P30 value, which represents the percentage of GFR values within 30% of the measured values. The results showed that the P30 value for MB-102 plasma GFR relative to iodixanol plasma GFR was 100%, with a 95% confidence interval (CI) of [96.5, 100], which was above the target value of 80%. - Phase III Clinical Trial:
This trial also used a single-group design, enrolling 249 participants divided into two cohorts: Cohort 1 included 130 participants with an estimated GFR (eGFR) ≥ 70 mL/min/1.73m² (normal to mildly impaired renal function), while Cohort 2 included 119 participants with eGFR < 70 mL/min/1.73m² (moderate to severe renal impairment). The primary efficacy endpoint was the P30 performance indicator of percutaneous GFR (tGFR) relative to plasma GFR (nGFR). Secondary endpoints included clearance (CL), body surface area (BSA), and pharmacokinetic parameters like area under the curve (AUC), maximum concentration (Cmax), and distribution volume. Safety endpoints included the safety of MB-102 and the TGFR system. The key inclusion criteria were adults with eGFR ranging from normal to CKD stage 4, with Fitzpatrick skin types I-VI. Exclusion criteria included eGFR > 120 mL/min/1.73m² or < 15 mL/min/1.73m².
The results showed that 243 participants completed the study (Cohort 1: 125, Cohort 2: 118). The P30 value for tGFR relative to nGFR was 94.0%, with a 95% CI of [89.4%, 96.9%], which exceeded the target of 85%. The median CL was 82.048 mL/min (range: 13.89, 151.64), the median BSA was 1.87 m² (range: 1.42, 2.52), the median nGFR adjusted for BSA was 76.886 mL/min/1.73m² (range: 12.31, 119.26), and the median tGFR was 69.174 mL/min/1.73m² (range: 11.38, 140.00). AUC ranged from 831.05 to 9216.78 min μg/mL, Cmax ranged from 6.87 to 40.19 μg/mL, and distribution volume ranged from 9897.24 to 24592.03 mL.
Regarding safety, 26 participants (10.4%) experienced adverse events, with a slightly higher incidence in Cohort 2 (12.6%) compared to Cohort 1 (8.5%). One participant (0.4%) in Cohort 1 experienced a moderate adverse event, while the rest were mild. No adverse events related to the study device, severe adverse events, unanticipated severe device-related events, or fatal events were reported.
In conclusion, the clinical data meets the current clinical evaluation requirements.
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