Drug Eluting Balloon Catheter_NMPA Approval in December 2017
Product Name: Drug Eluting Balloon Catheter
Category: Domestic Class III
Registration Pathway: Priority
NMPA Approval Time: December 2017
Product Structure and Composition: This product is an Rx type balloon dilatation catheter, consisting of a balloon, marker ring, distal shaft, proximal shaft, and catheter base. The distal shaft is coated with a polyethylene pyrrolidone coating and is divided into outer tube, inner tube, and tip tube. The balloon is made of Pebax7233, with a drug-coated surface containing paclitaxel at a dosage of 3.0μg/mm², with iohexol as the drug carrier. The product is for single-use.
Scope of Application: Dilating primary coronary artery bifurcation stenosis.
Working Principle: The product is delivered to the site of vascular lesions, where the balloon is inflated to mechanically dilate the narrowed part of the vessel. Post-vascular shaping procedures can lead to restenosis due to factors like excessive intimal proliferation. Paclitaxel can block early growth factors, inhibit cytoskeletal generation, block mitosis, suppress rapid cell proliferation, inhibit smooth muscle cell migration and phenotype changes, and suppress intimal proliferative inflammatory responses. Paclitaxel, mixed with iohexol, is sprayed onto the surface of the balloon to release the anti-proliferative drug paclitaxel locally on the coronary artery vessel wall, inhibiting excessive intimal proliferation.
Performance Research: Product performance evaluation includes drug dosage selection, interaction between paclitaxel, iohexol, and the device, balloon compliance, simulated use, coating uniformity, balloon expansion time and frequency, residual 2-chloroethanol, the effect of sterilization on the drug coating, among other studies.
Biocompatibility: This product is an externally connected device that comes into short-term contact with circulating blood. Biocompatibility evaluations were conducted according to the GB/T 16886 series standards, including biological tests such as cytotoxicity, delayed hypersensitivity reactions, intradermal irritation, acute systemic toxicity, hemolysis, thrombosis, coagulation, and pyrogen.
Sterilization: The product is provided in a sterile state and sterilized using ethylene oxide. Sterilization confirmation reports were provided, demonstrating a sterility assurance level of 10^-6. The residual ethylene oxide is not more than 10μg/g, and the average daily dose of residual 2-chloroethanol does not exceed 9mg.
Product Service/Shelf Life and Packaging: The product has a shelf life of two years. A verification report for the shelf life is provided, including real-time and accelerated aging verification, which includes product stability and packaging integrity verification.
Animal Experiment: The purpose of the experiment is to evaluate the drug release, product performance, and safety of the medical thrombus removal balloon catheter in a healthy porcine coronary artery model within 24 hours. Evaluation indicators include the balloon's ability to be pushed into the vessel, pass through the lesion site, degree of balloon expansion, balloon visibility, balloon wall adhesion performance, balloon retraction ability, hemostasis of the balloon introduction sheath, balloon-induced vascular dissection, balloon folding during pushing, overall evaluation of balloon use, residual drug amount after expansion, drug absorption by the target vessel, blood drug concentration, gross anatomical observations, TIMI blood flow, and pathological analysis.
Clinical Evaluation: The product undergoes clinical evaluation through clinical trials to assess its safety and effectiveness for dilating primary coronary artery bifurcation stenosis. The clinical trial is a prospective, multicenter, randomized controlled efficacy design. As there are currently no similar drug balloon products on the market, the control product chosen is a standard balloon dilatation catheter approved in China in 2016. The clinical trial is conducted in 10 clinical sites, with a total of 222 patients enrolled (113 in the trial group and 109 in the control group) with primary coronary artery bifurcation stenosis. The primary evaluation indicator is the degree of postoperative 270-day stenosis of the target lesion vessel lumen, with secondary evaluation indicators including immediate efficacy, rates of target lesion failure at 30, 180, and 270 days (TLF), target lesion revascularization rate (TLR), target vessel revascularization rate (TVR), and major adverse cardiac and cerebrovascular events (MACCE). The full analysis set (FAS) includes 222 patients, with 113 in the trial group and 109 in the control group; the per-protocol set (PPS) includes 174 patients, with 92 in the trial group and 82 in the control group; the safety set (SS) includes all 222 patients, with 113 in the trial group and 109 in the control group.
Note: To further observe the long-term safety and effectiveness of the product in the real world, the applicant should conduct post-market registration studies, with follow-up indicators including but not limited to surgical success rate, major adverse cardiac events, target lesion revascularization, target lesion failure rate, death, myocardial infarction, and thrombosis.