(114 days)
Not Found
No
The device description and performance studies focus on the material properties and biological interaction of a chitosan membrane for nerve repair, with no mention of AI or ML algorithms for analysis, diagnosis, or treatment.
Yes.
The device is intended for the "repair of peripheral nerve injuries" and acts as "an interface between the nerve and the surrounding tissue for uses to treat nerve injuries," directly indicating a therapeutic purpose.
No
NeuroShield is a medical device designed for the repair of peripheral nerve injuries, specifically a chitosan membrane that provides protection and acts as an interface for nerve and surrounding tissue. It is not used to diagnose a medical condition.
No
The device description clearly states that NeuroShield™ is a physical chitosan membrane, a tangible material intended for surgical implantation. It is not software.
Based on the provided information, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use is for the "repair of peripheral nerve injuries." This is a therapeutic intervention performed in vivo (within the body), not a diagnostic test performed in vitro (outside the body) on samples like blood or tissue.
- Device Description: The device is a "chitosan membrane to provide a non-constricting protection for peripheral nerves." This describes a physical barrier or support for tissue repair, not a reagent or instrument used to analyze biological samples for diagnostic purposes.
- Mechanism of Action: The description focuses on providing a physical interface and support for nerve regeneration, not on detecting or measuring substances in a biological sample.
- Performance Studies: The performance studies described are related to biocompatibility, mechanical properties, and in vivo performance in animal models of nerve repair. These are typical studies for implantable or therapeutic devices, not IVDs which would focus on analytical and clinical performance related to diagnosis.
In summary, the device's purpose, description, and evaluation methods clearly indicate it is a therapeutic device for nerve repair, not an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
NeuroShield[TM] is indicated 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.
Product codes (comma separated list FDA assigned to the subject device)
JXI
Device Description
NeuroShield™ is a chitosan membrane to provide a non-constricting protection for peripheral nerves. NeuroShield™ is designed to be an interface between the nerve and the surrounding tissue for uses to treat nerve injuries. When hydrated, NeuroShield™ is easy to handle, soft, pliable, nonfriable, porous and transparent. NeuroShield™ is provided as a sterile, non-pyrogenic rectangular sheet in the size of 40 x 30 x 0.03 mm and is intended for single use. NeuroShield™ is perforated to support the transport of physiological liquid through the wall of the device thereby easing the attachment to nerve tissue. With a diameter of 0.2 mm the holes make up 0.8% of the surface area of NeuroShield™. NeuroShield™ can easily be placed over the injured nerve, and can be sutured if necessary. Furthermore, the device can be trimmed or shaped to the appropriate size to fit the nerve tissue to be treated.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
peripheral nerves
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Under supervision of a healthcare professional
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The following studies were performed:
- Cytotoxicity: In vitro evaluation of cytotoxicity potential. Result: Only slight evidence of cell lysis or toxicity (grade 1), meeting requirements.
- Acute systemic toxicity: In vivo evaluation in mice. Result: No mortality or evidence of systemic toxicity.
- Sensitization: Evaluation of delayed dermal contact sensitization in guinea pigs. Result: No evidence of causing delayed dermal contact sensitization; not considered a sensitizer.
- Irritation/Intracutaneous reactivity: Evaluation in rabbits for irritation following intracutaneous injection. Result: Met requirements, with a mean score difference lower than 1.0.
- Systemic toxicity: Evaluation following subcutaneous implantation in rats. Sample size: 12 male and 12 female rats (6/sex/group for test and negative control). Result: No evidence of systemic toxicity.
- Implantation: In vivo evaluation of local tissue response in rabbit muscle tissue. Result: Macroscopic reaction was not significant; microscopically, classified as a moderate irritant.
- Pyrogenicity (USP): Evaluation for potential to induce a pyrogenic response following intravenous injection in rabbits. Result: Non-pyrogenic.
- Genotoxicity: Evaluation for potential to induce reverse mutations in bacterial strains. Result: Non-mutagenic.
- Hemolysis: Evaluation of hemolytic properties. Result: Mean hemolytic index of 0.0%; non-hemolytic.
- Mechanical and Physical Characteristics (Bench tests):
- Dimensional (visual inspection) and odor testing: Verified dimensions, color, and odor were within specified tolerances and comparable to predicate devices.
- Feel test after wetting: NeuroShield™ was found to be soft, pliable, and nonfriable, similar to predicate devices.
- Pliability around round surface: NeuroShield™ was found to be as pliable as predicate devices to wrap around round surfaces.
- Swelling and water uptake: NeuroShield™ fully hydrates in 10 minutes, similar to predicate devices.
- Suture retention strength test: NeuroShield™ has sufficient strength to resist suture pull-out.
- In vivo performance testing: Rat preclinical model for biocompatibility and performance in peripheral nerve repair, compared to Reaxon® Plus. Sample size: 17 adult female Wistar rats, divided into 6 groups.
- Groups: Nerves repaired with Reaxon® Plus (n=3, 2 weeks; n=3, 6 weeks; n=4, 12 weeks) and Neuroshield (n=4, 2 weeks; n=3, 6 weeks; n=4, 12 weeks).
- Methods: Functional analysis using grasping test; morphological analyses (light, confocal, electron microscopy) of regenerated nerve samples (number of myelinated fibers, axon and fiber diameter, myelin thickness, g-ratio); tissue reaction (multinucleated giant cells, ED1-immunopositive macrophages, polymorphonuclear cells, lymphocytes, plasma cells, neovascularization, fibrosis); degradation assessment.
- Result: Neuroshield allowed neuromuscular functional recovery equivalent to Reaxon® Plus. Immunohistochemical and electron microscopical analyses showed similar axon and glial cell presence, and colonization by regenerating fibers and Schwann cells. Morphoquantitative stereological analysis showed no statistical differences between groups. Similar tissue response observed. No statistical differences in ED1-immunopositive macrophages. Conclusion: Substantial equivalence between the two devices in repairing a 10 mm-long nerve gap. Beginning fragmentation observed at 12 weeks, with no signs of fibrosis or scar tissue.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found. Performance evaluation included:
- Cytotoxicity: Grade 1 (less than grade 2)
- Systemic Toxicity: No mortality or evidence of systemic toxicity
- Irritation/Intracutaneous reactivity: Mean score difference lower than 1.0 (0.0 and 0.3 for SC and SO test extracts)
- Hemolysis: Mean hemolytic index of 0.0%
- Suture retention test: Sufficient strength demonstrated.
- In vivo performance: No statistical differences between test and predicate devices in functional recovery and morphological metrics.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
May 31, 2019
Monarch Bioimplants GmbH Rivelino Montenegro, CEO Platz 4, Root, 6039 CH
Re: K190246
Trade/Device Name: NeuroShield Regulation Number: 21 CFR 882.5275 Regulation Name: Nerve Cuff Regulatory Class: Class II Product Code: JXI Dated: January 31, 2019 Received: February 6, 2019
Dear Rivelino Montenegro:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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) for
1
devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; 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 comprehensive regulatory information about medical devices and radiation-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,
Matthew Krueger, M.S.E. Assistant Director THT5A1: Neurosurgical Devices DHT5A: Division of Neurosurgical. Neurointerventional and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K190246
Device Name NeuroShield [TM]
Indications for Use (Describe)
Under supervision of a healthcare professional
· NeuroShield[TM] is indicated 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.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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Image /page/3/Picture/0 description: The image shows the logo for Monarch Bioimplants. The logo features the word "MONARCH" in a sans-serif font, with a stylized butterfly graphic above the "O". Below the word "MONARCH" is the word "BIOIMPLANTS" in a smaller, sans-serif font. The logo is a light blue color.
| A. Submitted by: | Monarch Bioimplants GmbH
Platz 4, CH-6039 Root D4, Switzerland
Phone: +41(0)41 4552261 / +41 (0)41 4552262
Fax: +41 (0)41 4552264
Email: mail@monarchbioimplants.com | |
|--------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| B. Date Prepared: | Apr/23/2019 | |
| C. Contact Person: | Dr. Rivelino Montenegro
CEO
Phone: +41(0)41 4552261 | |
| D. Product Name: | NeuroShieldTM | |
| E. Common Name: | Nerve Cuff | |
| F. Classification number/name: | 882.5275/Nerve Cuff | |
| G. Product Code: | JXI | |
| | | |
Section 5 - 510(k) Summary
H. Device description:
NeuroShield™ is a chitosan membrane to provide a non-constricting protection for peripheral nerves. NeuroShield™ is designed to be an interface between the nerve and the surrounding tissue for uses to treat nerve injuries. When hydrated, NeuroShield™ is easy to handle, soft, pliable, nonfriable, porous and transparent.
NeuroShield™ is provided as a sterile, non-pyrogenic rectangular sheet in the size of 40 x 30 x 0.03 mm and is intended for single use.
NeuroShield™ is perforated to support the transport of physiological liquid through the wall of the device thereby easing the attachment to nerve tissue. With a diameter of 0.2 mm the holes make up 0.8% of the surface area of NeuroShield™.
NeuroShield™ can easily be placed over the injured nerve, and can be sutured if necessary. Furthermore, the device can be trimmed or shaped to the appropriate size to fit the nerve tissue to be treated.
The picture below shows a sketch of NeuroShieldTM
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Image /page/4/Picture/0 description: The image shows the logo for Monarch Bioimplants. The logo features the word "MONARCH" in a sans-serif font, with a stylized butterfly icon above the "O". Below the word "MONARCH" is the word "BIOIMPLANTS" in a smaller, sans-serif font. The logo is a light blue color.
Section 5 - 510(k) Summary
Image /page/4/Figure/3 description: The image shows a rectangular breadboard with dimensions labeled as 30 mm and 40 mm. The breadboard is populated with numerous small, circular holes arranged in a grid pattern. These holes are likely connection points for electronic components. The breadboard is depicted at an angle, providing a three-dimensional perspective.
Picture 1. Sketch of NeuroShield™. A chitosan membrane of 30 x 40 x 0.03 mm with microscopic porosity.
I. Indications for Use:
Under supervision of a healthcare professional
- NeuroShield™ is indicated 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.
J. Predicate Device:
NeuroShield™ is substantially equivalent in function and intended use to:
| 510(k) number | Device name | Device company |
|---|---|---|
| K103081 | CovaTMORTHO-NERVE | Biom'Up Advance Biomaterials |
| K143711 | Reaxon® Plus | Medovent GmbH |
| K152967 | NerbridgeTM | Toyoba Co., Ltd. |
The predicate devices are described in more detail below:
- Cova"MORTHO-NERVE is a pure collagen membrane designed to be used as a barrier to allow guided healing along distinct anatomical planes. It is completely resorbable within a time frame that is compatible with healing. The membrane is obtained by standardized, controlled manufacturing processes. Cova™ORTHO-NERVE is further sterilized in double-pouches by gamma-irradiation.
Cova"MORTHO-NERVE membranes are designed to be resorbable, non inflammatory and biocompatible for uses to treat peripheral nerve injuries. When wetted, the membrane is conformable, elastic and easy to handle. It can be used alone or, if
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Section 5 - 510(k) Summary
needed, it can be sutured in place. Cova™ORTHO-NERVE is provided in rectangular sheets of 15 x 25 mm. 20 x 30 mm. 30 x 40 mm and 40 x 60 mm. Furthermore, the device can be easily trimmed or shaped to the appropriate size, without tearing or fragmenting, to fit the zone to be treated.
-
Reaxon® Plus is a flexible and transparent chitosan based implant designed for repair ● of peripheral nerve discontinuities up to 10 mm and where gap closure can be achieved by flexion of the extremity.
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. -
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 TM 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 104 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.
| Parameter | Device | Predicate Device | Predicate Device | Predicate Device |
|---|---|---|---|---|
| Device name | NeuroShield™ | Cova™ | ||
| ORTHO-NERVE | Reaxon® Plus | Nerbridge™ | ||
| Company Name | Monarch | |||
| Bioimplants | ||||
| GmbH | Biom'Up | |||
| Advance | ||||
| Biomaterials | Medovent GmbH | Toyoba Co., Ltd. | ||
| 510(k) # | K103081 | K143711 | K152967 | |
| Material | Chitosan | Collagen | Chitosan | Collagen and |
| Polyglycolic | ||||
| Acid |
A table of comparative features may be found below.
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Image /page/6/Picture/0 description: The image shows the logo for Monarch Bioimplants. The logo features the word "MONARCH" in a stylized font, with a circle containing butterfly silhouettes above the "O". Below the word "MONARCH" is the word "BIOIMPLANTS" in a smaller, simpler font. The color scheme is a light teal.
Section 5 - 510(k) Summary
| Indications
For Use | Indicated 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. | Indicated 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. | Reaxon® Plus is
indicated for
repair of peri-
pheral nerve
discontinuities up
to 10 mm and
where gap
closure can be
achieved by
flexion of the
extremity. | Indicated 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. |
|-------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Packaging | Double pouch | Double blister | Double blister | Foil double
pouch within
protective outer
pouch |
| Physical
structure | Membrane,
rollable if needed | Membrane,
rollable if needed | Tube | Cylindrical |
| Sterilization
Method | EO | Gamma
irradiation | EO | EO |
In vitro and in vivo biocompatibility testing according to ISO 10993 standards and bench tests, have been performed on NeuroShield™. These tests proved that NeuroShield™ is as safe as, and performs as well as its legally marketed predicate devices Cova™ORTHO-NERVE, Reaxon® Plus and Nerbridge™.
Below there is a summary of each study that was performed.
Cytotoxicity
Purpose: To evaluate in vitro the cytotoxicity potential of NeuroShield™
Method: A single preparation of the test article was extracted in single strength Eagle Minimum Essential Medium (EMEM 10) at 37 ± 1℃ for 72 hours. This article was placed on triplicate sub-confluent monolayers of L-929 mouse fibroblast cells. Separate monolayers were prepared for triplicate negative and positive controls. After incubating at 37 ± 1℃ in 5 ± 1% C02 for 48 ± 2 hours, the cultures were stained with a trypan blue solution. The cultures were then examined microscopically to determine cell morphology. Result: Only slight evidence of cell lysis or toxicity (grade 1). 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 appropriate test article extract was injected into a group of five mice. Similarly, a separate group of five mice was dosed with each corresponding
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Section 5 - 510(k) Summary
extraction vehicle alone (control blank). The mice 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 at 24, 48 and 72 hours after injection.
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 (SC) and sesame oil (SO). Each extract was intradermally injected (induction I) and topically applied (induction II) to ten test guinea pigs (per extract) in an attempt to induce delayed sensitization. The extraction was similarly injected and topically applied to five control blank guinea pigs (per vehicle). Following recovery period, the test and control blank animals received a challenge patch of the appropriate test article extract and the extraction vehicle. All sites were scored at 24 (± 2) and 48 (± 2) 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: The test article was extracted in 0.9% sodium chloride (SC) and sesame oil (SO). 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 three rabbits. Similarly, the extract vehicle alone (control blank) was injected on the right side of the back of each rabbit. The injection sites were observed immediately after injection. Observations for erythema and edema were conducted at 24, 48, and 72 hours after injection.
Result: Under the conditions of the study, the test article met the requirements of the test since the difference between each test extract overall mean score and corresponding control blank overall mean score was lower than 1.0 (0.0 and 0.3 for the SC and SO test extracts.
Systemic toxicity
Purpose: To evaluate for the potential to cause systemic toxicity.
Method: Twelve male and 12 female rats were randomly assigned to either the test or negative control group (6/sex/group). Rats were observed daily for overt signs of toxicity. Detailed clinical examinations were conducted weekly. Rats were weighed prior to implantation, at weekly intervals, the day prior to termination and on the day of euthanasia. After 4 weeks, blood samples were collected for hematology and clinical chemistry analysis and the rats were euthanized. A necropsy was conducted, selected
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Section 5 - 510(k) Summary
organs were collected and weighed. A microscopic evaluation of the collected organs was conducted.
Result: Under the conditions of this study, there was no evidence of systemic toxicity from the test article following subcutaneous implantation of NeuroShield™ in the rat.
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 moderate irritant as compared to the negative control article.
Pyrogenicity (USP)
Purpose: To evaluate for the potential to induce a pyrogenic response following intravenous injection in rabbits based on the United States Pharmacopeia (USP 39 - NF 34).
Method: The test article was extracted in 0.9% sodium chloride (SC). A 10 mL/kg dose of the appropriate test article was intravenously injected to 3 rabbits. Rectal temperature was measured every 30 minutes for 3 hours after injection.
Result: Non-pyrogenic. Under the conditions of the study, the test article met requirements of the USP 39 - NF 34. The test article was judged as non-pyrogenic.
Genotoxicity
Purpose: To evaluate for the potential to induce reverse mutations at the histidine locus of the Salmonella typhimurium tester strains TA98, TA1535 and TA1537 or at the tryptophan locus of Escherichia coli tester strain WP2uvrA in a bacterial reverse mutation assav.
Method: The test article was extracted in 0.9% sodium chloride (SC) and in dimethyl sulfoxide (DMSO). The assay was conducted in the presence and absence of metabolic activation.
A preliminary dose range finding (DRF) assay was firstly conducted on 5 doses of the SC and DMSO test article extract (100%, 50%, 12.5% and 6.25%, v/v), on the Salmonella typhimurium LT2 TA100 tester strain and Escherichia coli tester strain WP2uvrA in the absence and presence of metabolic activation using the direct incorporation method to find the suitable nontoxic dose of the extracts to be tested in mutagenicity assay. For both SC and DMSO extracts, the highest nontoxic dose was
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Image /page/9/Picture/0 description: The image shows the logo for Monarch Bioimplants. The logo features the word "MONARCH" in a sans-serif font, with a stylized butterfly graphic incorporated into the "O". Below the word "MONARCH" is the word "BIOIMPLANTS" in a smaller, sans-serif font. The color scheme is a light teal.
Section 5 - 510(k) Summary
found to be 100 uL/plate of the 100% (v/v) extract, both in the absence and presence of metabolic activation.
Tubes containing molten top agar were inoculated with culture from one of the five tester strains, along with the test article extracts tested at the single dose of 100 uL/plate of the 100% extract. An aliquot of phosphate buffer or rat liver S9 Mixture providing metabolic activation was added. The mixture was poured across triplicate plates. Parallel testing was conducted with control blank and positive controls. The mean number of revertants for the test extract plates was compared to the mean number of revertants of the appropriate control blank plates for each of the five tester strains.
Result: Non-mutagenic. The SC and DMSO test article extract were considered to be nonmutagenic to S. typhimurium tester strains TA98, TA100, TA1535, and TA1537, and to E. coli WP2uvrA tester strain.
Hemolysis
Purpose: To evaluate the hemolytic properties of the material.
Method: Blood was obtained from human, pooled, diluted, and added to triplicate tubes with the calcium and magnesium-free Dulbecco's phosphate buffered saline (CMF-DPBS) test article extract. These combinations were evaluated to determine whither extract of the test article would cause in vitro red blood cell hemolysis. Control blanks, negative control and positive controls were prepared in the same manner as the test article. The tubes were then maintained for at least 3 hours at 37 ± 2℃ with gentle periodic inversions at approximately 30 minutes intervals. Following incubation, suspensions vere mixed gently and centrifuged. The resulting supernatant was added to Drabkin's reagent. The absorbances of the solutions were spectrophotometrically measured at the wavelength of 540 nm.
Result: Under the conditions of this study, the mean hemolytic index for the test article extract was of 0.0%. The test article extract was non hemolytic.
Based on the results presented above we conclude that NeuroShield™ is as safe as its predicate devices for its intended use.
Performance Characteristics
The mechanical and physical characteristics (bench tests) of NeuroShield™ were evaluated in a series of tests. These tests were conducted to ensure that NeuroShield1M possess the mechanical and physical properties that determine its suitability for use in the human body. Testing has demonstrated that the nerve cuff is able to hold a suture and to be placed around surfaces.
These tests were done in direct comparison to the NeuroShield™ predicate devices Cova™ORTHO-NERVE and Reaxon® Plus.
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Section 5 - 510(k) Summary
Dimensional (visual inspection) and odor testing
Purpose: To verify that the dimensions of NeuroShield™ were within specified tolerances as indicated in the packaging in comparison to the predicate devices. The color and odor were also registered.
Method: Direct measurement of the dimensions of the membranes as well direct comparison to the predicate devices.
Result: Dimensional analysis was completed to verify that the dimensions of NeuroShield™, color and odor were within specified tolerances of the indicated values and in comparison to the predicate devices.
Feel test after wetting
Purpose: The purpose of the feel test is to observe whether the product is soft and stable enough in the hands of a surgeon, who has to handle, fold or trim the device before implanting it.
Methods: After wetting in PBS for 10 minutes the samples are handled as a surgeon would do in a real case before implanting. It is important to observe if the device is soft and pliable (to be folded, rolled, etc.) and whether it can be handled and clamped with tweezers without breaking in pieces (nonfriable).
Result: The feel test (handling) showed that NeuroShield™ is as soft, pliable and nonfriable as the predicate devices Cova™ORTHO-NERVE and Reaxon® Plus.
Pliability around round surface
Purpose: The purpose of this test is to check the ability of the device to wrap around round surfaces such as nerves.
Method: After wetting in PBS for 10 minutes the samples are placed around rods of different diameters.
Result: NeuroShield™ is as pliable as its predicate devices Cova™ORTHO-NERVE and Reaxon® Plus to wrap around round surfaces as for example nerve cables.
Swelling and water uptake
Purpose: To check how fast the swelling takes places and the change in dimensions. This is important since NeuroShield™ and its predicate devices Cova™ORTHO-NERVE and Reaxon® Plus are hydrogels and require aqueous environment to become completely soft and of ease handling. The recommended time in contact with saline solution before implantation is 10 minutes, therefore this test checks whether the swelling and water update is almost complete in the first 10 minutes of contact with aqueous solution.
Method: The devices were placed in PBS (pH 7.4) at room temperature, while the length and width (or inner diameter) were measured in different time intervals. The samples were also weighed (g) at the respective time intervals (10 minutes, 2, 3 and 24 hours).
Result: NeuroShield114 needs only 10 minutes in contact with aqueous solution to be fully hydrated, similarly to its predicate devices.
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Section 5 - 510(k) Summary
Suture retention strength test
Purpose: The purpose of the retention strength test was to verify that NeuroShield™ has sufficient strength to resist suture pull-out under loads exceeding the ones anticipated in the intended use environment.
Method: After 24 hours in PBS (pH 7.4) at room temperature, the devices were incubated for 1 hour at 37°C for the measurement of suture retention.
For this measurement, the devices had one extremity clamped at the lower clamp of a mechanical tester.
A suture thread (USP 6/0 Prolene) was used to pierce the devices (NeuroShield1M and Cova™ORTHO-NERVE were folded for the needle to pierce through two walls, while Reaxon® Plus was pierced twice across the diameter of the tube) at 2 mm from the top extremity and the suture was clamped at the top clamp of the mechanical tester.
The force required to pull out the thread at constant cross-head speed of 1 mm/min was monitored.
Result: Suture retention strength testing was completed to verify that NeuroShield™ has sufficient strength to resist suture pull-out under loads exceeding those anticipated in the intended use environment.
In vivo performance testing
Purpose: The aim of this project was to conduct an in vivo study in a standardized rat preclinical model to demonstrate that a novel chitosan device (Neuroshield) has similar biocompatibility and performance properties in the peripheral nerve repair as the chitosan device Reaxon® Plus.
Methods: The functional animal study was performed with 17 adult female Wistar rats, weighing approximately 200 g. Median nerves were repaired with Reaxon® Plus and NeuroShield and harvested at 2, 6 and 12 weeks. The animals were divided in the following experimental groups:
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Nerves repaired with Reaxon® Plus for 2 weeks (n=3);
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Nerves repaired with Neuroshield for 2 weeks (n=4).
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Nerves repaired with Reaxon® Plus for 6 weeks (n=3);
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Nerves repaired with Neuroshield for 6 weeks (n=3);
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Nerves repaired with Reaxon® Plus for12 weeks (n=4);
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Nerves repaired with Neuroshield for 12 weeks (n=4).
Functional analysis was performed on rats at 2, 6 and 12 weeks using the grasping test in order to evaluate the functional recovery of finger flexor muscles after median nerve reconstruction.
The regenerated nerve samples were harvested 2, 6 and 12 weeks after the surgery and morphological analyses by light and confocal microscopy, as well as electron microscopy, were carried out in order to evaluate the nerve regeneration, including the number of myelinated fibers, axon and fiber diameter, myelin thickness and g-ratio. In addition, the tissue reaction was investigated by evaluating the presence of multinucleated giant cells and activated ED1-immunopositive macrophages, as well as polymorphonuclear cells,
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Image /page/12/Picture/0 description: The image shows the logo for Monarch Bioimplants. The logo features the word "MONARCH" in a sans-serif font, with a stylized butterfly graphic incorporated into the "O". Below the word "MONARCH" is the word "BIOIMPLANTS" in a smaller, sans-serif font. The color scheme is a light teal.
Section 5 - 510(k) Summary
lymphocytes, plasma cells, neovascularization, and fibrosis of the tissue at and surrounding the treatment site.
Degradation was assessed based on the amount of absorbable material left at the implant site, as well as material parameters, such as fragmentation and/or debris presence, form and location of remnants of degraded material, and by a histological assessment of the tissue at and surrounding the treatment site.
Result: Behavioral analysis on rats of both experimental groups evaluated after median nerve repair demonstrated that Neuroshield allowed neuromuscular functional recovery equivalent to Reaxon® Plus. Immunohistochemical and electron microscopical analyses carried out inside the two conduits showed that few axons, together with glial cells are already present after two weeks in both conduits; at 6 and 12 weeks the conduits are both colonized by regenerating fibers and Schwann cells. Morphoquantitative stereological analysis showed no statistical differences between the two experimental groups. Additionally, a similar tissue response was observed for both devices. Moreover, no statistical differences were found as regards the number of ED1-immunopositive macrophages in Neuroshield at 6 and 12 weeks, confirming steady state conditions. In conclusion, altogether the results revealed a substantial equivalence between the two devices in repairing a 10 mm-long nerve gap of the rat median nerve.
Beginning fragmentation of NeuroShield was observed at 12 weeks post-implantation, and fragments were detected within the regenerating tissue and in the surrounding connective tissue.
The thickness of the membrane has decreased significantly compared to the 2 weeks animals, which is in consistency with the significant mass loss observed in the in vitro testing as result of enzymatic degradation. Regenerated fibers and blood vessels occurred according to the time and progress of the regeneration process. There were no signs of fibrosis or scar tissue being formed around the degrading material.
K. Conclusion:
NeuroShield™ is intended for use in repair of peripheral nerve discontinuities and where gap closure can be achieved by flexion of the extremity.
Based on the results of animal studies, in vitro product characterization studies, in vitro and in vivo biocompatibility and performance studies, we conclude that NeuroShield™ is as safe as, and substantially equivalent to its predicate devices.