(258 days)
Nerbridge™ is intended for the repair of peripheral nerve injuries in which there is no gap or where a gap closure can be achieved by flexion of the extremity.
Nerbridge™ is a product composed of polyglycolic acid and collagen derived from porcine skin. Nerbridge™ is a flexible, resorbable and semipermeable tubular membrane matrix filled with porous collagen that provides a non-constricting encasement for injured peripheral nerves for protection of the neural environment. Nerbridge™ is designed to be an interface between the nerve and the surrounding tissue. When hydrated, Nerbridge™ is a pliable, soft, non-friable, porous conduit. The resilience of Nerbridge allows the product to recover and maintain closure without constricting the nerve once the device is placed around the nerve. Nerbridge™ is manufactured using validated viral inactivation and removal processes for the collagen. The product is provided in a foil pouch, sterile, nonpyrogenic, for single use only, in a variety of sizes, and placed in an outer Tyvek header bag for added protection.
This document describes the regulatory acceptance of a medical device, Nerbridge™, a nerve cuff for peripheral nerve repair. It does not describe an AI/ML powered device, so several of the requested sections regarding AI/ML acceptance criteria and studies (e.g., sample size for test/training sets, data provenance, number of experts, adjudication method, MRMC comparative effectiveness study, standalone performance) are not applicable.
Below is the information derived from the provided text, focusing on the acceptance criteria and the studies performed for the Nerbridge™ device.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Nerbridge™ device were primarily based on a series of non-clinical (functional performance, product characterization, biocompatibility) and clinical studies designed to demonstrate its safety and effectiveness, and substantial equivalence to predicate devices. The table below summarizes the non-clinical tests and their acceptance criteria, as reported in the document.
| Test | Test Method Summary | Acceptance Criteria Met? |
|---|---|---|
| Suture retention strength | Testing according to ISO 7198:1998 | Yes |
| Mechanical compression & rebound | Testing according to JIS T0401:2013 | Yes |
| Porosity | Testing according to ISO 845:2006 and JIS Z8807:2012 | Yes |
| Permeability | Devices filled with protein solution, immersed in saline, protein measured in saline. | Yes |
| In vitro degradation | Testing according to ISO 15814:1999 and ISO 527-1:2012 | Yes |
| Tensile strength | Testing according to ISO 527-1:2012 | Yes |
| pH | Testing according to JIS T 3211:2011 | Yes |
| Swelling rate | Testing according to ISO 10545-3:1995 | Yes |
| Visual inspection | Visual inspection with a magnifying glass. | Yes |
| Bending stiffness | Testing according to JIS T0401:2013 | Yes |
| Endotoxin | Testing according to Japanese Pharmacopoeia 16th edition and FDA Guidance for Industry: Pyrogen and Endotoxin Testing: Questions and Answers (June 2012) | Yes |
Biocompatibility Testing:
| Test | Test Method Summary | Results/Acceptance |
|---|---|---|
| Cytotoxicity | ISO Direct contact Cytotoxicity Assay | Non-cytotoxic |
| Sensitization | ISO Guinea pig Maximization test with device extracts (saline and sesame oil extracts) | No evidence of sensitization |
| Acute intracutaneous Reactivity | ISO Acute intracutaneous Reactivity Test in rabbits with device extracts (saline and sesame oil extracts) | No evidence of irritation |
| Acute Systemic Toxicity | ISO Acute System Toxicity in Mice with device extracts (saline and sesame oil extracts) | No mortality or evidence of systemic toxicity |
| Rabbit Pyrogen Study | USP Material-mediated Rabbit pyrogen test with saline extract of the device | No evidence of material-mediated pyrogenicity |
| Hemolysis | Hemolysis test by direct contact with human red blood cells | No hemolytic activity |
| Genotoxicity (Ames Mutagenicity Assay) | ISO Ames Mutagenicity Assay with device extracts (saline and ethanol extracts) | No evidence of mutagenicity |
| Genotoxicity (Mouse bone marrow) | ISO Mouse bone marrow micronucleus with device extracts (saline and sesame oil extracts) | No evidence of clastogenicity |
| Genotoxicity (CHL/IU cells) | CHL/IU cells with device extracts (MEM & 10%CS/MEM) | No evidence of inducing chromosomal aberrations or polyploid cells |
| Implantation Absorption | Subcutaneous implantation in rats | Absorption of material by 13 weeks. No inflammation observed |
| Implantation (safety & performance) | In vivo safety and performance study in rats after 3, 30 and 90 days | Protection during nerve repair. No fibrous peri-nervous tissue was observed after 3, 30 or 90 days. |
| Subchronic / Chronic toxicity | 13-week systemic toxicity and local tolerance study in rats following subcutaneous implantation | No adverse tissue reaction to the implant up to 13 weeks of implantation. No systemic toxicity. |
Clinical Study Acceptance:
The primary efficacy endpoint was a higher mean percentage of improvement in the sensory function test by the Semmes-Weinstein method for the Nerbridge™ device compared to the autogenous free nerve grafting group. The incidence of adverse events was lower for the Nerbridge™ device. This indicated that the device was safe and effective for its intended use and substantially equivalent to predicate devices.
2. Sample Size Used for the Test Set and the Data Provenance
-
Clinical Study Test Set:
- Sample Size: 60 subjects for the Nerbridge™ device (Full Analysis Set: 58 subjects, Per Protocol Set: 54 subjects). The control group consisted of 6 subjects.
- Data Provenance: Multi-center (20 trial sites), joint randomized, evaluator-blinded, comparative clinical study. The country of origin of the data is not explicitly stated but implies a controlled clinical trial environment. It was a prospective study.
-
Animal Study Test Set:
- Sample Size: Not explicitly stated, but performed in a "rabbit model."
- Data Provenance: Not explicitly stated, but implies a controlled animal study environment. It was a prospective animal study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This information is not explicitly detailed in the provided document, as the evaluations primarily involved objective measurements (e.g., sensory function tests, histological examinations, physical/chemical property testing). For the clinical study, an "evaluator-blinded" design was used, implying trained evaluators for the sensory function test, but their specific qualifications or number are not specified.
4. Adjudication Method for the Test Set
Not applicable/specified. The clinical study was evaluator-blinded, implying objective assessment rather than a consensus-based adjudication in the way it might be for image interpretation. The non-clinical tests rely on predefined methods and acceptance criteria.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This device is a physical medical device (nerve cuff), not an AI/ML-powered or image interpretation device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Not applicable. This is not an algorithm.
7. The Type of Ground Truth Used
- Clinical Study: The "ground truth" for the clinical study was based on objective measures of nerve repair and function, specifically the "mean percentage of improvement in primary evaluation in the sensory function test by the Semmes-Weinstein method," and the "incidence of adverse events." This could be considered outcomes data and validated clinical assessment.
- Animal Study: The ground truth involved histological reactions at the site of device introduction and evidence of nerve regeneration, which is a form of pathology/histological assessment and outcomes data (biological response).
- Non-Clinical/Biocompatibility Studies: The ground truth was based on established industry standards (ISO, JIS, USP, FDA guidance) and validated test methods for material properties and biological interactions.
8. The Sample Size for the Training Set
Not applicable. This is not an AI/ML device that requires a training set.
9. How the Ground Truth for the Training Set was Established
Not applicable. This is not an AI/ML device.
§ 882.5275 Nerve cuff.
(a)
Identification. A nerve cuff is a tubular silicone rubber sheath used to encase a nerve for aid in repairing the nerve (e.g., to prevent ingrowth of scar tissue) and for capping the end of the nerve to prevent the formation of neuroma (tumors).(b)
Classification. Class II (performance standards).