The NMPA granted innovation approval to Boston Scientific Neuromodulation’s DBS directional lead and issued a review report on November 6.
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 a compatible implantable deep brain stimulator and extension lead to deliver electrical stimulation pulses. It provides stimulation to the bilateral subthalamic nucleus (STN) for the adjunctive treatment of certain symptoms in mid-to-late-stage levodopa-responsive Parkinson’s disease that cannot be effectively controlled by medication. It also provides stimulation to the bilateral internal segment of the globus pallidus (GPi) for the adjunctive treatment of certain symptoms in late-stage levodopa-responsive Parkinson’s disease that are inadequately managed by medication. The implantable deep brain stimulation system, comprising this product, the compatible neurostimulator, and extension lead, is classified as an MRI-safe medical device under specific magnetic resonance conditions. Under stipulated conditions, and provided that special protective measures are taken for the patient and the implanted equipment, the patient can undergo clinical MRI scanning at a field strength of 1.5T.
- Model/Specification
- Working principle
This product is used in combination with an implantable deep brain neurostimulator and extension lead. The implantable neurostimulator delivers electrical pulses to targeted deep brain areas via the extension lead, providing adjunctive treatment. The product features a 1-3-3-1 segmented design, allowing for directional electrical stimulation by adjusting specific segmented electrodes that can be turned on or off.
Pre-clinical
- Product Performance Studies
The applicant established specific product performance standards covering appearance, size, X-ray detectability, corrosion resistance, sterility, bacterial endotoxin levels, residual ethylene oxide, DC resistance, tensile load, bending fatigue, chemical properties, electrode wire connection strength, insertion and removal force, electrode leakage current, compatibility of parts, as well as electrical safety and electromagnetic compatibility. Supporting documentation was submitted, including product performance research data, technical specifications, and testing reports. The results complied with the established product specifications.
- Biocompatibility Studies
Given the product’s prolonged contact with human tissue, biocompatibility was evaluated according to the GB/T 16886.1-2022 standard, Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing in the Risk Management Process. Evaluations covered cytotoxicity, intracutaneous reaction, sensitization, pyrogenicity, acute systemic toxicity, subchronic toxicity, subacute toxicity, implantation, genotoxicity, chronic toxicity, and carcinogenicity. All evaluations met regulatory requirements.
- Sterilization Studies
Key product components, such as electrodes, cranial electrode lock caps, supplementary tool kits, tunneling tools, torque wrenches, and connection cables, are provided in a sterile condition, utilizing ethylene oxide sterilization. The applicant submitted a sterilization validation report confirming that the product’s sterility assurance level (SAL) meets required standards, with ethylene oxide residue levels not exceeding 10 μg/g.
- Product Shelf Life and Packaging
The product has a shelf life of 24 months. Documentation supporting shelf-life efficacy, usage duration, and packaging validation was provided, which confirmed compliance with requirements.
- Safety in Magnetic Resonance Environments
The applicant submitted studies evaluating the product’s safety in magnetic resonance imaging (MRI) environments based on the product’s technical characteristics. The assessment confirmed that under specified conditions, the product poses an acceptable level of residual risk for MRI compatibility.
- Animal Studies
The applicant conducted a 90-day animal study using a chronic pig model with a sample size of 20 pigs. The study involved clinical observations and laboratory tests, followed by anatomical analysis, pathological examination, and product assessment post-removal. Results indicated no clinically significant histological changes attributable to the directional electrode stimulation compared to the control group. The product demonstrated expected performance and met safety standards.
- Relevant Standards Compliance
The product complies with standards GB 16174.1-2015, GB9706.1-2020, and YY 9706.102-2021.
Clinical
The applicant conducted a clinical trial to evaluate the safety and efficacy of the DBS electrode, targeting Parkinson’s disease (PD) symptoms. They submitted data from a prior product, an 8-contact standard electrode, to establish a comparative basis for safety and effectiveness. This study was a prospective, multicenter, double-blind, adaptive, randomized controlled trial in the United States, involving 23 institutions and initially targeting 310 participants. Ultimately, 160 participants were enrolled, with 121 in the treatment group and 39 in the control group, and both the intention-to-treat (ITT) and per-protocol (PPS) populations were analyzed.
Key inclusion criteria for participants included a diagnosis of idiopathic Parkinson’s disease with symptoms lasting five years or more, Hoehn-Yahr stage of at least 2, and motor complications occurring for at least six hours daily despite optimal drug therapy. Participants were randomly assigned to a treatment or sham group to assess the product’s efficacy.
The primary endpoint was the duration of time each day without motor complications at the 12-week mark post-treatment. Results showed significant improvements, with the treatment group having a mean difference in motor complication-free time compared to the control group, achieving the trial’s superiority criteria. Secondary endpoints included changes in several quality-of-life and Parkinson’s-specific scales, such as UPDRS (Unified Parkinson’s Disease Rating Scale) scores, PDQ-39 (Parkinson’s Disease Questionnaire), and CGI (Clinical Global Impression). The treatment group consistently showed statistically significant improvements across these measures over the control group.
Regarding safety, the study reported a low rate of serious adverse events (0.7%) linked to the stimulation, similar to those in comparable DBS devices already on the market. Additional subgroup analysis showed that both early and late-stage Parkinson’s patients responded to the device similarly, with no substantial group differences in the primary outcome.
To further demonstrate the new product’s reliability and applicability, the applicant included non-clinical data such as a VTA (volume of tissue activation) simulation, showing directional stimulation met the design’s safety and efficacy targets. Animal studies on 20 pigs were also conducted, comparing tissue response at 90 days post-implantation between the new and prior products, finding no significant differences.
Additionally, a post-market, international, open-label observational registry study across 43 centers in 12 countries evaluated the DBS product in real-world settings. With 971 enrolled participants, primary outcomes indicated a significant improvement in PDQ-39 scores from baseline to 26 weeks post-implantation, which was sustained for two years. Similarly, MDS-UPDRS III scores, which assess motor function, improved significantly and remained stable over two years. Both patient and clinician CGI assessments showed sustained improvement over time. Data from a subgroup of patients who received DBS in the GPi target area indicated that improvements in PDQ-39 scores were comparable to those observed in patients treated with STN-DBS.
Overall, the study results indicate that the new DBS product provides a safe and effective treatment for Parkinson’s motor symptoms, comparable to existing DBS products while offering sustained quality-of-life improvements over time.
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