The NMPA granted innovation approvals to CryoLife, Inc’s BioGlue Surgical Adhesive 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
The product is intended for open surgical repair of large blood vessels (such as the aorta, femoral artery, and carotid artery) in adult patients and can be used as an adjunct to standard hemostatic methods (such as sutures and needles).
- Model/Specification
- Working principle
Pre-clinical
- Product Performance Studies
The performance evaluation of the product includes several tests beyond the basic technical requirements. These tests cover various aspects, such as the concentration of methanol in glutaraldehyde, impurity analysis related to glutaraldehyde, the heat absorption/release properties during the BSA (bovine serum albumin) and glutaraldehyde cross-linking process, post-polymerization BSA determination, residual glutaraldehyde post-polymerization, and degradation studies. Results from these studies demonstrate that the product meets the input design requirements.
- Biocompatibility
Since the product is a permanent implant that comes into contact with tissue and tissue fluids, it underwent a comprehensive biocompatibility evaluation based on the GB/T 16886 series of standards. Various tests were conducted, including cytotoxicity, sensitization reaction, intracutaneous reaction, genetic toxicity, blood compatibility, implantation, subchronic toxicity, acute systemic toxicity, and pyrogen tests. For the accessories, additional tests like cytotoxicity, sensitization, intracutaneous reaction, hemolysis, and acute toxicity were performed. All results showed that the product’s biocompatibility risks are acceptable.
- Sterilization
The submitted product consists of a pre-filled syringe and accessories, which include standard mixing tubes, tip applicator mixing tubes, and tip extension mixing tubes. Sterilization methods vary for different components: the pre-filled syringe, standard mixing tube, and tip applicator mixing tube are sterilized using gamma rays, while the tip extension mixing tube is sterilized with ethylene oxide. The applicant provided sterilization validation reports, demonstrating that the sterility assurance level post-sterilization reaches 10⁻⁶.
- Product Shelf Life and Packaging
The product includes a pre-filled syringe and various accessories. The sterilization shelf life for different syringe models (BG3510-5, BG3502-5, and BG3515-5) is 24 months, 21 months, and 18 months, respectively, while the accessories have a shelf life of 60 months. The applicant provided both accelerated aging and real-time aging validation reports. Additionally, compatibility verification studies were carried out following the guidelines for compatibility studies between chemical drugs and packaging materials.
- Animal Studies
Animal testing was conducted on a pig model to evaluate the product’s performance in preclinical trials. The study focused on the product’s degradation over 365 days (1 year), its local effects after implantation, systemic toxicity, clotting and thrombogenic potential, and other clinical adverse events. The results confirmed that the product met the expected design requirements and performed as anticipated.
Clinical
The applicant conducted a clinical trial to evaluate the safety and efficacy of the product. The trial was designed as a prospective, multi-center, randomized controlled, non-inferiority study. It was conducted at 7 clinical trial institutions, with 182 patients randomly enrolled. Of these, 182 patients were included in the ITT (Intent-to-Treat) population, 174 in the safety population, and 164 in the PP (Per-Protocol) population.
Clinical trial results: When BioGlue was used to assist structural repair and hemostasis in Chinese patients with acute type A aortic dissection, the intraoperative false lumen closure success rate reached 98.84%. The results indicate that the trial met its primary endpoint, demonstrating that the efficacy of BioGlue was not inferior to conventional surgical repair. Furthermore, there was no clinically significant difference in safety between the use of BioGlue and conventional surgical repair in Chinese patients with acute type A aortic dissection.
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