(89 days)
Reaxon Plus is indicated for repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity.
Reaxon® Plus is a flexible and transparent chitosan based implant designed for repair of peripheral nerve discontinuities.
Reaxon® Plus was developed to provide a protective environment for axonal growth across a nerve gap. When hydrated, Reaxon® Plus is an easy to handle, soft, pliable, transparent chitosan tube. Reaxon® Plus is provided sterile, non-pyrogenic, for single use in double blister packages in a variety of sizes as shown below.
Here's an analysis of the provided text to extract information regarding acceptance criteria and the study proving the device meets them:
Disclaimer: The provided document is a 510(k) summary for a medical device (Reaxon® Plus, a nerve guide). Unlike a typical clinical trial report for an AI/ML diagnostic, this document focuses primarily on demonstrating substantial equivalence to a predicate device, largely through biocompatibility and mechanical testing, and then references a separate clinical trial for performance. Therefore, many of the typical acceptance criteria and study details for an AI/ML algorithm (e.g., algorithm-only performance, MRMC studies, detailed ground truth establishment for a diagnostic output) are not directly applicable or fully detailed in this type of submission. This response will extract what is present and note where information is not available due to the nature of the document.
Device Name: Reaxon® Plus (Nerve Guide)
Predicate Device: NeuraGen® Nerve Guide
1. Table of Acceptance Criteria and Reported Device Performance
Since this is a nerve guide (physical implant) and not an AI/ML diagnostic, the "acceptance criteria" are related to biocompatibility, mechanical properties, and clinical performance for nerve regeneration, rather than diagnostic metrics like sensitivity/specificity. The document states that the new device has "similar safety and effectiveness as its predicate device."
| Acceptance Criteria Category | Acceptance Criteria (General) | Reported Device Performance (Reaxon® Plus) |
|---|---|---|
| Biocompatibility (ISO 10993) | No toxicity, irritation, sensitization, genotoxicity, or pyrogenicity; suitable local tissue response. | Cytotoxicity: No cytotoxicity (Grade < 2). Acute Systemic Toxicity: No mortality or evidence of systemic toxicity.Sensitization: No evidence of delayed dermal contact sensitization.Irritation/Intracutaneous Reactivity: No irritation.Subacute Toxicity: No evidence of systemic toxicity; non-irritant.Implantation: Non-irritant local tissue response compared to negative control at 12 weeks.Pyrogenicity: Non-pyrogenic (total rise of rabbit temperatures within USP limits).Genotoxicity: Non-mutagenic (Bacterial Reverse Mutation Study, Mouse Lymphoma Assay, Mouse Peripheral Blood Micronucleus Study showed no mutagenic/chromosomal damage effects). |
| Mechanical/Physical Properties | Maintain dimensions after sterilization; sufficient suture retention; withstand compression and rebound. | Dimensional/Visual Inspection: Dimensions within specified tolerances after EO sterilization.Suture Retention Strength Test: Sufficient strength to resist suture pull-out under loads exceeding anticipated use (specific value not given, but "exceeding those anticipated in the intended use environment" implies acceptance).Compression and Rebound Analysis: Can withstand compressive forces >0.25N and re-open following removal of compressive forces (specific rebound measurement implied satisfactory). |
| Long-Term Stability/Degradation (Animal) | Slow, mild degradation; good stability; mild tissue response. | Slow degradation process; very mild tissue response. Low number of activated macrophages, good stability, marginal signs of degradation until 50 weeks, first significant macroscopic signs at 74/77 weeks. Stable biological tissue response at 3 months, further decreasing macrophages and thinner fibrotic layer. |
| Clinical Performance (Nerve Regeneration) | Achieve meaningful nerve regeneration for peripheral nerve discontinuities, including larger gaps. | Demonstrated nerve regeneration in finger nerve defects, including gaps up to 26 mm. Static 2-PD: 50% of Reaxon® group achieved meaningful response (grade 2 or 3) at 6 months vs. 20% of control (autograft).Moving 2-PD: 50% of Reaxon® group and 60% of control showed response (grade 2 or 3) at 6 months; 33% of Reaxon® had best score (grade 3) vs. 20% of control.Semmes-Weinstein Monofilaments: 33% of Reaxon® group vs. 60% of control achieved normal/diminished perception of light touch at 6 months. No Reaxon® patients showed no sensation (grade 0), while 20% of control did.Pain/Safety: Comparable pain/satisfaction/discomfort. 4 AE in test group, 2 in control; mostly moderate. One AE (wound dehiscence) in test group related to device (moderate severity). |
Note on "Acceptance Criteria": For the clinical performance aspect, the document doesn't define strict quantitative acceptance criteria (e.g., "s2-PD must be X or better in Y% of patients"). Instead, it compares the Reaxon® Plus (referred to as "Reaxon" in the clinical evaluation section) to the "gold standard autologous nerve grafting" and concludes that Reaxon® could provide faster nerve regeneration and showed positive results even for larger than 10 mm gaps. The "acceptance" is implicitly tied to demonstrating comparable or superior performance to the predicate/gold standard.
2. Sample Size Used for the Test Set and Data Provenance
- Biocompatibility/Mechanical Tests: Sample sizes are not explicitly stated for individual tests (e.g., how many samples were tested for suture retention), but methodologies describe using "triplicate monolayers," "group of five animals," "ten test guinea pigs," "three animals," etc.
- Long-term Animal Implantation: Wistar rats (specific number of animals or implants not given, though "after different implantation times (12, 24, 50 and 74/77 weeks)" implies multiple animals over time).
- Clinical Evaluation:
- Test Set Sample Size: 11 subjects (for the interim report). This small sample included 6 patients in the Reaxon® group and 5 patients in the Autograft (control) group.
- Data Provenance: The clinical trial used for the clinical evaluation of Reaxon® (which is stated to be "exactly the same nerve guide as Reaxon® Plus") was done in Europe (as suggested by the European approval mentioned). It appears to be a prospective clinical study, as it describes a "first interim clinical study report" with follow-up points at 3 and 6 months after inclusion of the first subject (inclusion of first subject until 31.12.2016).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- This question is not directly applicable to this device submission. For a physical implant like a nerve guide, "ground truth" for clinical performance is established by objective measurements of nerve function (e.g., 2-point discrimination, monofilament tests) and clinical outcomes, not expert consensus on image interpretation.
- The clinical trial collected objective measures of nerve regeneration and patient-reported outcomes.
4. Adjudication Method for the Test Set
- Not applicable in the typical sense for AI/ML diagnostics. Clinical trial data typically involves data collection by trained personnel at clinical sites following a protocol. It doesn't involve "adjudication" in the sense of resolving conflicting expert opinions on a diagnostic output. Data consistency and quality are typically managed through standard clinical trial monitoring and quality control processes.
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
- No, an MRMC study was not done. This is a physical implant, not an AI-assisted diagnostic tool for human readers. The clinical study was a direct comparison of the device (Reaxon®) to traditional autografting for nerve repair.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Not applicable. This device is a physical nerve guide implant. There is no algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
-
Clinical Outcomes Data and Objective Measurements: For the clinical evaluation, the "ground truth" for nerve regeneration and function was established through:
- Static 2-point discrimination (s2-PD) measurements.
- Moving 2-point discrimination (m2-PD) measurements.
- Semmes-Weinstein monofilament test results (for sensory reinnervation).
- Pain assessment.
- Assessment of adverse events (safety).
- Comparison to the "current gold standard autologous nerve grafting."
-
Bench and Animal Testing: For the non-clinical tests, the "ground truth" was derived from standard laboratory and animal model evaluations based on established scientific methods and relevant ISO standards (e.g., ISO 10993 for biocompatibility) and direct physical measurements for mechanical properties.
8. The sample size for the training set
- Not applicable. This is not an AI/ML device that requires a training set. The various pre-clinical tests (biocompatibility, mechanical) demonstrate performance of the manufactured device.
9. How the ground truth for the training set was established
- Not applicable. As there is no training set for an AI/ML algorithm, this question is not relevant. The "ground truth" for the device's design and performance claims is rooted in established scientific principles, ISO standards, and the results of the described pre-clinical and clinical studies.
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Image /page/0/Picture/0 description: The image shows the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. Food & Drug Administration" in blue text.
April 24, 2018
Medovent GmbH Peter Meier CEO Friedrich-Koenig-Str. 3 Mainz, DE 55129
Re: K180222
Trade/Device Name: Reaxon Plus Regulation Number: 21 CFR 882.5275 Regulation Name: Nerve Cuff Regulatory Class: Class II Product Code: JXI Dated: August 21, 2017 Received: January 25, 2018
Dear Dr. Meier:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820);
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and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Michael J. Hoffmann -S
Carlos L. Peña. PhD. MS for Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K180222
Device Name Reaxon Plus
Indications for Use (Describe)
Reaxon Plus is indicated for repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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| MEDOVENT GmbHImplants that careFriedrich-Koenig-Str. 3, D-55129 Mainz - GermanyTel. +496131-61769-0, Fax +496131-6176929mail@medovent.com | ||
|---|---|---|
| 510(k) Summary(as required by 21 CFR 807.92) | Page 1 of 13 | |
| A. Submitted by: | MEDOVENT GmbHFriedrich-Koenig-Str. 3D-55129 Mainz GermanyPhone: +49 6131 617 690Fax: +49 6131 617 6929mail@medovent.com | |
| B. Date Prepared: | Mar/29/2018 | |
| C. Contact Person: | Dr. Peter MeierCEOPhone: + 49 6131 617 690 | |
| D. Product Name: | Reaxon® Plus | |
| E. Common Name: | Nerve Guide | |
| F. Classification number/name: | 21 CFR 882.5275, Nerve Cuff | |
| G. Product Code: | JXI |
H. Device description:
Reaxon® Plus is a flexible and transparent chitosan based implant designed for repair of peripheral nerve discontinuities.
Reaxon® Plus was developed to provide a protective environment for axonal growth across a nerve gap. When hydrated, Reaxon® Plus is an easy to handle, soft, pliable, transparent chitosan tube. Reaxon® Plus is provided sterile, non-pyrogenic, for single use in double blister packages in a variety of sizes as shown below.
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510(k) Summary
Page 2 of 13
(as required by 21 CFR 807.92)
| Item number | RP321 | RP330 | RP340 | RP350 | RP360 |
|---|---|---|---|---|---|
| Inner diameter (mm) | 2.1 | 3.0 | 4.0 | 5.0 | 6.0 |
| Length (mm) | 30 | 30 | 30 | 30 | 30 |
| Item number | RP121 | RP130 | RP140 | RP150 | RP160 |
| Inner diameter (mm) | 2.1 | 3.0 | 4.0 | 5.0 | 6.0 |
| Length (mm) | 14 | 14 | 14 | 14 | 14 |
| Schematics of the ID(mm) of each size | Image: small circle | Image: small circle | Image: medium circle | Image: large circle | Image: larger circle |
| Real picture of eachmodel of Reaxon®Plus. | Image: tubes |
Reaxon® Plus is indicated for repair of peripheral nerve discontinuities and where gap closure can be achieved by flexion of the extremity.
I. Intended Use:
Under supervision of a healthcare professional
- Reaxon® Plus is indicated for repair of peripheral nerve discontinuities where gap ● closure can be achieved by flexion of the extremity.
J. Predicate Device:
Reaxon® Plus is substantially equivalent in function and intended use to:
- NeuraGen® Nerve Guide, which is a tubular device designed for repair of peripheral nerve . discontinuities. Like the predicate device, Reaxon® Plus is provided sterile, for single use only. Reaxon® Plus and NeuraGen® Nerve Guide are both manufactured from
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(as required by 21 CFR 807.92)
bioresorbable materials. Reaxon® Plus meets the ISO 10993 requirements for biocompatibility.
| Parameter | Device | Predicate Device |
|---|---|---|
| Device name | Reaxon® Plus | NeuraGen® Nerve Guide |
| Company Name | Medovent GmbH | Integra LifeSciences Corporation |
| 510(k) # | K180222 | K011168 |
| Material | Chitosan | Collagen |
| Indications For Use | Repair of peripheral nervediscontinuities where gapclosure can be achieved byflexion of the extremity. | Repair of peripheral nervediscontinuities where gapclosure can be achieved byflexion of the extremity. |
| Packaging | Double blister | Double blister |
| Sterilization Method | EO | EO |
A table of comparative features can be found below.
As indicated in the table of comparative features above, the difference between Reaxon® Plus and the predicate device is the material. As Reaxon® Plus is based on chitosan, the predicate device is based on collagen. Both chitosan and collagen are natural, animalderived polymers that are biocompatible and biodegradable. In both Reaxon® Plus and the predicate device, the material is processed into sterile tubular nerve guides.
Given the difference between Reaxon® Plus and the predicate device, in vitro and in vivo biocompatibility testing according to ISO 10993 standards, long term implantation and bench tests on Reaxon® Plus have been performed to be used to establish substantial equivalence. These tests proved that Reaxon® Plus has a similar safety and effectiveness as its predicate device NeuraGen® Nerve guide.
Below there is a summary of each study that was performed.
Cytotoxicity
Purpose: To evaluate the in vitro cytotoxicity potential of Reaxon® Plus.
Method: A single preparation of the test article was extracted in single strength Minimum Essential Medium (IX MEM) at 37°C for 24 hours. Triplicate monolayers of L-929 mouse fibroblast cells were dosed with each extract and incubated at 37°C in the presence of 5% CO2 for 48 hours. Following incubation, the monolayers were examined microscopically for abnormal cell morphology and cellular degeneration.
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Tel. +496131-61769-0. Fax +496131-61 mail@medovent.com
Result: No cytotoxicity. No evidence of cell lysis or toxicity. The test article extract met the requirements of the test since the grade was less than a grade 2 (mild reactivity).
Acute systemic toxicity
Purpose: To evaluate for acute systemic toxicity in mice.
Method: A single dose of the extract of the test article was injected into a group of five animals, which were observed for signs of systemic toxicity immediately after injection and at 4, 24, 48 and 72 hours after injection. Body weights were recorded prior to dosing and on days 1, 2 and 3.
Result: There was no mortality or evidence of systemic toxicity from the extracts injected into mice. Each test article extract met the requirements of the study.
Sensitization
Purpose: To evaluate the potential of the test article to cause delayed dermal contact sensitization in the guinea pig maximization test.
Method: The test article was extracted in 0.9% sodium chloride USP and sesame oil, NF. Each extract was intradermally injected and occlusively patched to ten test guinea pigs (per extract). The extraction vehicle was similarly injected and occlusively patched to five control guinea pigs (per vehicle). Following a recovery period, the test and control animals received a challenge patch of the appropriate test article extract and the vehicle control. All sites were scored for dermal reactions at 24 and 48 hours after patch removal
Result: The test article extracts showed no evidence of causing delayed dermal contact sensitization in the guinea pig. The test article was not considered a sensitizer in the guinea pig maximization test.
Irritation/Intracutaneous reactivity
Purpose: To evaluate for the potential to cause irritation following intracutaneous injection in rabbits.
Method: A 0.2 mL dose of the appropriate test article extract was injected intracutaneously into five separate sites on the right side of the back of each of three animals. The injection sites were observed immediately after injection. Observations for erythema and edema were conducted at 24, 48, and 72 hours after injection.
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Result: No irritation. The test article met the requirements of the difference between each test extract overall mean score and corresponding control overall mean score was 0.0 and 0.2 for the Sodium chloride and Sesame Oil test extracts, respectively.
Subacute toxicity
Purpose: The test articles were surgically implanted in rats to evaluate the potential systemic toxicity and local tissue response at the implantation site.
Method: Animals were observed for overt signs of toxicity. Detailed clinical examinations were conducted at pretreatment, weekly and at termination. A microscopic evaluation of the implantation sites and collected organs was conducted.
Result: No subacute toxicity. There was no evidence of systemic toxicity from the test article following subcutaneous implantation in the rat. The test article was classified as non-irritant as compared to the control article.
Implantation
Purpose: To evaluate the local tissue response of the test article implanted in muscle tissue of the rabbit.
Method: The test article and negative control were intramuscularly implanted and animals were euthanized 12 weeks later. Muscle tissues were excised and the implant sites examined macroscopically. A microscopic evaluation of representative implant sites from each animal was conducted to further define any tissue response.
Result: The macroscopic reaction was not significant as compared to the negative control article. Microscopically, the test article was classified as a non-irritant as compared to the negative control article.
Pyrogenicity
Purpose: To evaluated in the rabbit the potential mediated pyrogenicity.
Method: A single dose of 10 mL/kg was intravenously injected via the marginal ear vein into each of three animals. Rectal temperatures were measured and recorded prior to injection and at 30 minute intervals between 1 and 3 hours after injection.
Result: Non-pyrogenic. The total rise of rabbit temperatures during the 3 hour observation period was within acceptable USP limits. The test article was judged as non-pyrogenic.
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drich-Koenig-Str. 3. D-55 Tel. +496131-61769-0. Fax +496131-61 mail@medovent.com
Genotoxicity
BacterialReverseMutationStudy
Purpose: To evaluate whether a test article extract would cause mutagenic changes in Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537, and Escherichia coli tester strain WP2uvrA in the presence and absence of mammalian metabolic activation.
Method: Tubes containing molten top agar were inoculated with culture from one of the five tester strains, along with the DMSO or saline extract. An aliquot of sterile water for injection or rat liver S9 homogenate, providing metabolic activation, was added. The mixture was poured across triplicate plates. Parallel testing was conducted with negative controls (extraction vehicle alone) and positive controls. The mean number of revertants for the test extract plates was compared to the mean number of revertants of the negative control plates for each of the five tester strains.
Result: The DMSO and saline test article extracts were considered to be nonmutagenic to S. typhimurium tester strains TA98, TA100, TA1535, and TA1537, and Escherichia coli tester strain WP2uvrA.
MouseLymphomaAssay
Purpose: To evaluate whether the test article extract induced gene mutations and chromosomal damage in mammalian cells.
Method: The test article was soaked in sufficient volume (100 mL for the extraction in DMSO and 500 mL for the extraction in RPMI0) of 0.9% sodium chloride (SC) to fully cover and submerge the sample. The test article was soaked for 10 minutes. The test article was removed from the saline, weighed, placed in a tightly capped vial, and delivered to the laboratory for immediate extraction. The test article and each of the negative controls (extraction vehicle without the test article) were subjected to the extraction. The RPMIo extract was supplemented to a 3% serum concentration prior to the 4 hour treatments and to a 10% serum concentration for the 24 hour treatment. The DMSO extract was diluted to a final concentration of 1.0% with RPMI3 for the 4 hour treatments and with RPMI0 for the 24 hour treatment. Each test extract and the negative control were tested in duplicate.
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Result: The RPMI0 and DMSO test article extracts did not cause a two-fold or greater increase in the mean mutant frequency of the L5178Y/TK* cell line either in the presence or absence of metabolic activation. The test article was not mutagenic.
MousePeripheralBloodMicronucleusStudy
Purpose: To evaluate the potential for a test article extract to cause damage to chromosomes or the mitotic apparatus of murine erythroblasts by measuring the frequency of micronucleated reticulocytes (MN-RETs) in mice. Erythroblasts are erythrocyte precursor cells in the bone marrow.
Method: The test article was soaked in a sufficient volume (90 mL) of 0.9% sodium chloride (SC) to fully cover and submerge the sample. The test article was soaked for 10 minutes. The test article was removed from the saline, weighed, placed in a tightly capped vial, and delivered to the laboratory for immediate extraction. Twenty two or twenty three test articles were used for each extraction. The test article was subjected to the following extraction conditions: 50°C for 72 hours. The extracts were continuously agitated during extraction. Fresh extracts were prepared for each day of dosing.
For three consecutive days, twelve mice per test article extract (six per sex) were injected intraperitoneally with the test article extracts. Similarly, six animals per sex were dosed with either the appropriate vehicle as the negative control or methyl methanesulfonate as a positive control. All animals were observed immediately following dosing and daily for assessment of general health. On day 4, blood was collected from the tail veins and reticulocytes were evaluated for the presence of micronuclei by flow cytometry.
Result: The test article extracts did not induce micronuclei in mice.
Long term implantation of Reaxon® Plus
Purpose: To evaluate the long term stability and tolerance of the implanted Reaxon® Plus.
Method: Reaxon® Plus was implanted in Wistar rats in a 10 mm rat sciatic nerve defect. After different implantation times (12, 24, 50 and 74/77 weeks) Reaxon® Nerve Guide was explanted and properties of the tubes, the connective tissue as well as the nerve cable analyzed to evaluate tissue reactions and the stability of the implanted nerve guide.
Results: The study demonstrated a slow degradation process and very mild tissue response after implantation of Reaxon® Plus. The analysis revealed a low number of activated macrophages at the implantation site of Reaxon® Plus showing low degradation activity
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in the chitosan tubes with good stability and only marginal signs of degradation until 50 weeks and first significant macroscopic signs of degradation at time point 74/77 weeks. The biological tissue response to Reaxon® Plus was found to be stable already at 3 months post-implantation, confirmed by the small and further decreasing number of macrophages and thickness of the fibrotic layer at the site of implantation which are indicators for a very mild tissue response.
Based on the results presented above we conclude that Reaxon® Plus has a similar safety as its predicate device NeuraGen® Nerve Guide.
Performance Characteristics
The mechanical and physical characteristics (bench tests) of the Reaxon® Plus were evaluated in a series of tests. These tests were conducted to ensure that Reaxon® Plus has the mechanical properties (suture retention and mechanical compression strength) as well as physical properties that determine their suitability for use in the human body. Testing has demonstrated that the nerve guides are able to hold a suture and resist repeated compression from surrounding tissues.
These tests were done in direct comparison to Reaxon® Plus predicate device NeuraGen® Nerve Guide.
Dimensional / Visual Inspection
Purpose: To evaluate the influence of ethylene oxide sterilization on the dimensions of Reaxon® Plus.
Method: Direct measurement of the dimensions of the tubes before and after sterilization.
Result: Dimensional analysis was completed to verify that the dimensions of Reaxon® Plus were within specified tolerances following ethylene oxide sterilization.
Suture Retention Strength Test
Purpose: To evaluate the suture retention strength of Reaxon® Plus.
Method: After 24 hours in PBS (pH 7.4) at RT, the tubes were incubated for 1 hour at 37°C for the measurement of suture retention. One extremity of the tube was fixed at the lower clamp of the mechanical tester. A suture thread (USP 6/0 Prolene) was used to pierce the tube at 2 mm of the top extremity (in both sides of the extremity) and the suture
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510(k) Summary
was fixed at the top clamp of the mechanical tester. The force required to pull out the thread at constant cross-head speed at 1 mm/min was monitored.
Result: Suture retention strength testing was completed to verify that Reaxon® Plus has sufficient strength to resist suture pull-out under loads exceeding those anticipated in the intended use environment.
Compression and Rebound Analysis
Purpose: To evaluate the compression and rebound properties of Reaxon® Plus.
Method: A transverse compression test was performed. After incubating the tubes for 1 h at 37°C, 1 cm of each tube was tested. A displacement perpendicular to the longitudinal axis of the conduit was applied at a crosshead speed of 1 mm/min to a final displacement of approximately 60 % of the diameter of the conduits. The force "F" versus displacement "d" is recorded.
Result: Compression and rebound analysis was completed to verify that Reaxon® Plus can withstand compressive forces greater than 0.25N and it will re-open following removal of compressive forces sufficient to collapse the nerve cuff.
Clinical evaluation of Reaxon® Plus for gaps above 10 mm
To prove that Reaxon® Plus can be used to nerve gaps up above 10 mm as shown in the animal tests, we would like to summarize the results from a clinical trial using Reaxon® Nerve Guide, which is approved in Europe and it exactly the same nerve guide as Reaxon® Plus.
This first interim clinical study report summarizes preliminary data regarding safety and performance of the chitosan-based nerve guide Reaxon® to bridge nerve defects in fingers in comparison with an autologous nerve graft. Preliminary data were obtained from 11 subjects who concluded the 6 months follow-up visit until 31.12.2016 (18 months after inclusion of the first subject).
As it can be seen from the report, patients with gaps up to 26 mm received Reaxon® to bridge the nerve gap.
The primary variable of this investigation is the static 2-point discrimination (s2-PD). A meaningful response six months after surgery was achieved by 50% of the test group and 20% of the control group. Evaluation of s2-PD measurements pointed out that
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Image /page/12/Picture/0 description: The image shows a document with the title "510(k) Summary" and the text "(as required by 21 CFR 807.92)". The document also includes the email address "mail@medovent.com". The page number is "Page 10 of 13". The document also includes the company logo and address for MEDOVENT GmbH.
subjects treated with Reaxon show better results in nerve regeneration than subjects treated with autograft (figure 1).
Evaluation of moving 2-PD measurements showed similar results in both groups. 50% of the test group and 60% of the control group showed a response (grade 2 or 3) 6 months after surgery. However, the best score (grade 3) was achieved by 33% of the Reaxon® group and 20% of the control group (figure 2).
Image /page/12/Figure/3 description: The image is a stacked bar graph comparing Reaxon and Autograft treatments over time. The y-axis represents percentages from 0% to 100%, while the x-axis shows time points BL (baseline), 3M (3 months), and 6M (6 months) for each treatment. The graph displays the distribution of different grades (Grade 0- to Grade 3) based on s2-PD measurements, with each grade represented by a different color.
Figure 1: Static 2-PD measurements. The measured 2-PD [mm] was assigned to different grades.
Grade 0 (poor); grade 1 (fair); grade 2 (good); grade 3 (excellent). Scores of 2 or 3 were evaluated as (meaningful) response. At a score of 0 it was determined if the subject has protective sensibility (0+) or is anesthetic (0-). BL = base line visit; 3M = 3 months follow-up visit; 6M = 6 months follow-up visit.
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Image /page/13/Figure/0 description: The image shows a document with the header "510(k) Summary" and the text "(as required by 21 CFR 807.92)". The document also includes the company name "MEDOVENT GmbH" and contact information such as the address "Friedrich-Koenig-Str. 3, D-55129 Mainz - Germany", telephone and fax numbers "+496131-61769-0, +496131-6176929", and email address "mail@medovent.com". The page number is indicated as "Page 11 of 13".
Image /page/13/Figure/1 description: The image is a stacked bar chart comparing Reaxon and Autograft treatments with sample sizes of N=6 and N=5, respectively. The chart displays the percentage distribution of different grades (Grade 3: m2-PD < 6mm, Grade: m2-PD 6-10mm, Grade 1: m2-PD 11-15mm, Grade 0: m2-PD > 15mm) at baseline (BL), 3 months (3M), and 6 months (6M). The Reaxon treatment shows a shift from Grade 0 at baseline to a mix of grades at 3M and 6M, while the Autograft treatment maintains a high percentage of Grade 0 at baseline, with a shift towards higher grades at 3M and 6M. The y-axis represents percentages ranging from 0% to 100%.
Figure 2: Moving 2-PD measurements. The measured m2-PD [mm] was assigned to different grades.
Grade 0 (poor); grade 1 (fair); grade 2 (good); grade 3 (excellent). Scores of 2 or 3 were evaluated as response. BL = base line visit; 3M = 3 months follow-up visit; 6M = 6 months follow-up visit.
Semmes-Weinstein monofilaments were utilized to assess sensory reinnervation. 33% of the test group and 60% of the control group got back normal or diminished perception of light touch 6 months after surgery. One subject of the control group (20 %) had no ability to sense any of the utilized monofilaments (grade 0) while none of the Reaxon® patients showed such results (figure 3).
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Image /page/14/Figure/0 description: The image shows a document with the title "510(k) Summary" and the text "(as required by 21 CFR 807.92)". The document also includes the address "Friedrich-Koenig-Str. 3, D-55129 Mainz", the telephone and fax numbers "Tel. +496131-61769-0, Fax +496131-6176929", and the email address "mail@medovent.com". The document is labeled as "Page 12 of 13" and includes the company logo for MEDOVENT GmbH.
Image /page/14/Figure/1 description: The image is a stacked bar chart comparing Reaxon and Autograft at 3 months and 6 months. The y-axis is in percentage from 0% to 100%, and the x-axis shows the time points 3 months and 6 months for both Reaxon (N=6) and Autograft (N=5). The bars are stacked to show the distribution of different categories, labeled as 5+, 5, 4+, 4, 3+, 3, 2+, 2, 1+, 1, and 0. The percentages for each category at each time point are indicated on the bars.
Figure 3: Semmes-Weinstein Monofilament test results at 3 months and 6 months follow-up visits. The recognized monofilament sizes were assigned to different grades. Grade 5 = filament 2.83 (normal perception of light touch); grade 4 = filament 3.61 (diminished perception of light touch); grade 3 = filament 4.31 (diminished protective sensation); grade 2 = filament 4.56 (no protective sensation); grade 1 = filament 6.65 (perception of deep pressure); grade 0 = no sensation; "+" indicates that the specific stimulus was recognized with certainty. The helping lines indicate a cut-off grade <4 and <2.
Pain assessment showed that most of the subjects had no pain or just slight pain 6 months after surgery. Only 1 patient of the autograft group rated the pain as "heavy". The evaluation of satisfaction and discomfort did not point out clear differences between both groups.
Safety data regarding peri- and post-surgery complications, medical observations and discomforts were comparable in both groups. Adverse events (AE) occurred in both treatment groups. There were 2 AE in the control group and 4 AE in the test group. The majority of AE was rated as moderate. Only one AE in the control group (intolerable pain) was rated as severe. In one case the AE (reopening of wound dehiscence) was stated to be related to the investigational medical device. Severity was assessed as "moderate"
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dverse events occurred in the test group. In both cases, causality was not assumed to the a
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Image /page/16/Picture/0 description: The image shows the logo for MEDOVENT GmbH. The logo is in black and gold, with the words "MEDOVENT GmbH" in bold letters. Below the company name is the tagline "Implants that care" in a smaller, gray font. The "O" in MEDOVENT is replaced with a gold circle.
Friedrich-Koenig-Str. 3, D-55129 Mainz - Germany
Tel. +496131-61769-0, Fax +496131-6176929
mail@medovent.com
The results of this first interim analysis indicate that an application of the chitosan based nerve guide Reaxon® could provide faster nerve regeneration than the current gold standard autologous nerve grafting. Safety data demonstrate good tolerance and compatibility of Reaxon® Nerve Guide. The positive results even for larger than 10 mm gaps (up to 26 mm), show that Reaxon® can be used for such large gaps.
K. Conclusion:
Reaxon® Plus is indicated for repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity.
Reaxon® Plus is flexible to accommodate movement of joint while retaining its shape and it is resistant to occlusive forces from surrounding tissue.
Reaxon® Plus has sufficient strength to resist suture pull-out under loads exceeding those anticipated in the intended use environment.
Biocompatibility studies have demonstrated Reaxon® Plus to be non-cytotoxic, nonsensitizing, non-pyrogenic and non-genotoxic.
Clinical results have shown that Reaxon® Plus can be successively used for nerve gaps over 10 mm.
Based on the results of animal studies, in vitro product characterization studies, in vitro and in vivo biocompatibility studies and clinical results we conclude that Reaxon® Plus has a similar safety and effectiveness profile as its predicate 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).