(102 days)
NerveTape is indicated for the repair of peripheral nerve discontinuities where can be achieved by flexion of the extremity.
The proposed BioCircuit Technologies, Inc. NerveTape device is composed of a bioabsorbable, extracellular collagen matrix (small intestinal submucosa, SIS) with integrated microhooks made of a nickel-titanium alloy, commonly referred to as NiTiNOL (identical to the predicate), for mechanical fixation and apposition of nerve ends. The NerveTape is implanted around an injured nerve to provide a scaffold which becomes infiltrated and remodeled by the patient's cells. The device protects the damaged or severed nerve while the nerve heals.
The device is packaged and supplied sterile in a clamshell container inside a sealed pouch. The device is identical to the predicate, except for the SIS substrate manufacturer and the addition of a smaller size. The dimensions of the finished device range from 11mm x 12mm x 22mm. The device is intended for the repair of nerves of diameters ranging from 1.5mm to 7mm.
Here is an analysis of the provided text regarding the NerveTape device, focusing on acceptance criteria and supporting studies:
1. Table of Acceptance Criteria and Reported Device Performance
| Test | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Performance Verification: Ease of Use (Simulated Use in Cadaver) | Product possesses acceptable characteristics for handling, trimming, and implantation. | The handling characteristics of the subject device are substantially equivalent or superior to the predicate device based on acceptability to the end-user. All samples met acceptance criteria. |
| Performance Verification: Monotonic Tensile Strength | Repair strength as assessed via device retention strength on repaired cadaveric nerve in comparison to standard suture repair according to the literature. | The ultimate tensile strength of the proposed device nerve repairs is substantially equivalent or superior to the predicate device. All samples met acceptance criteria. |
| Specification Compliance | Compliance with go/no-go dimensional and visual inspection criteria for all components and assemblies. | All samples met acceptance criteria. |
| Biocompatibility: Cytotoxicity (ANSI/AAMI/ISO 10993-5) | Test article extract's cytotoxic potential assessed by change in morphology of cell line. | The proposed device met the requirements of the test. (and for SIS material: met the requirements of the test, and cell viability/cytotoxic potential determined by XTT dye method met requirements) |
| Biocompatibility: Irritation (ANSI/AAMI/ISO 10993-23) | Potential for the proposed device/SIS material to produce irritation from intradermal injections. | The proposed device met the requirements of the test. (and for SIS material: met the requirements of the test and is a non-irritant) |
| Biocompatibility: Skin Sensitization (ANSI/AAMI/ISO 10993-10) | Potential for the proposed device/SIS material to invoke a dermal skin sensitization reaction in guinea pigs. | The proposed device met the requirements of the test. (and for SIS material: met the requirements of the test and is not considered to be a contact skin sensitizer) |
| Biocompatibility: Systemic Toxicity (Acute) (ANSI/AAMI/ISO 10993-11) | Potential for the proposed device/SIS material to produce acute systemic toxicity from a single dose administered by IV and IP injection. | The proposed device met the requirements of the test. (and for SIS material: met the requirements of the test) |
| Biocompatibility: Sterilization Residuals (ANSI/AAMI/ISO 10993-7) | Reported values of sterilant gas residue compared against the ISO standard for acceptable limits for permanent implants. | The proposed device met the requirements of the test. |
| Biocompatibility: Bacterial Endotoxins Test (BET) (ANSI/AAMI ST72, USP <161>, etc.) | Acceptable detected endotoxins must not exceed the maximum allowable limit for permanent implants. | The proposed device met the requirements of the test. |
| Biocompatibility: Systemic Toxicity (Subacute/Subchronic) (for SIS material only) (ANSI/AAMI/ISO 10993-11) | Potential for the SIS material to produce systemic toxicity from repeated exposure via dual route in rats over at least 14 days. | There is no potential toxicity of the SIS material from repeated exposure based on toxicological endpoints evaluated. |
| Biocompatibility: Pyrogenic Response (for SIS material only) (ANSI/AAMI/ISO 10993-11) | Potential for the SIS material to produce a pyrogenic response due to intravenous exposure (no increases in temperature of 0.5℃ or more). | The SIS material met the requirements of the test. |
| Biocompatibility: Genotoxicity (In Vitro Micronucleus Test) (for SIS material only) (ANSI/AAMI/ISO 10993-3) | Potential for extract of SIS material to induce micronuclei or hypodiploidy in cultured CHO cells. | The SIS material extract did not induce micronuclei or hypodiploidy and met the requirements of the test. |
| Biocompatibility: Genotoxicity (Bacterial Mutagenicity Test - Ames Assay) (for SIS material only) (ANSI/AAMI/ISO 10993-3) | Potential for extract of SIS material to induce gene mutations in bacteria. | The SIS material extract did not elicit evidence of bacterial mutagenicity and met the requirements of the test. |
| Biocompatibility: Local Effects After Implantation (Acute Intramuscular, 4 weeks) (for SIS material only) (ANSI/AAMI/ISO 10993-6) | Histological evaluation to determine if SIS material is well tolerated compared to control. | The SIS material was well tolerated in comparison to the control article and met the requirements of the test. |
| Biocompatibility: Local Effects After Implantation (Chronic Intramuscular, 16 weeks) (for SIS material only) (ANSI/AAMI/ISO 10993-6) | Histological evaluation to determine if SIS material is well tolerated compared to control. | The SIS material was well tolerated in comparison to the control article and met the requirements of the test. |
| Histological Comparison (SIS material only) | Absence of nuclei and cytoplasmic material, integrity of collagen network, and level of α-gal antigen in decellularized tissue compared to native tissue. | The decellularization process removed microscopic evidence of intact cells and nuclei, and preserved the collagen network. |
| Sterilization Validation | Conformance with ISO 11135:2014 and AAMI TIR28:2016 for Ethylene Oxide sterilization. | Pass |
| Animal Study (Tibial Nerve Implantation) | Proposed device meets all acceptance criteria and is substantially equivalent or superior to the predicate device. | The proposed device met all acceptance criteria and was substantially equivalent or superior to the predicate device. |
2. Sample Size Used for the Test Set and the Data Provenance
- Performance Verification (Ease of Use, Monotonic Tensile Strength): The text states "All samples met acceptance criteria," implying a sample size was used for these tests, but the exact number of samples is not specified.
- Biocompatibility Testing:
- Device Biocompatibility (largest size, sterile product): "all testing performed on sterile product of largest size" – implies at least one sample of the largest size was used for each test. Specific sample numbers (e.g., number of mice, rabbits, cell samples) are mentioned within the individual test summaries (e.g., "rabbits" for irritation, "guinea pigs" for sensitization, "mice" for systemic toxicity) but not a precise cumulative number.
- Decellularized Porcine Small Intestine Submucosa (SIS) Biocompatibility (raw material): "all testing performed on non-sterile, decellularized porcine small intestine raw material - SIS" – similar to device testing, specific animal counts are mentioned for relevant tests.
- Animal Studies: "a statistically valid number of rabbits" underwent implantation. The exact number of rabbits is not specified beyond being "statistically valid."
- Data Provenance: The studies are non-clinical (laboratory/animal studies). The biological components (porcine SIS) originate from pigs. The testing appears to be conducted in a controlled lab setting, not specified by country, but implies in-house or contracted lab testing for regulatory submission. All studies are prospective tests conducted on the device/material.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
There is no information provided regarding experts establishing "ground truth" in the traditional sense for these non-clinical, performance, and biocompatibility tests. The "ground truth" for these tests is based on established scientific standards (e.g., ISO, AAMI, USP protocols) and objective measurements or observations (e.g., cell morphology, tensile strength, histological evaluation, chemical quantification). For the "Ease of Use" test, "acceptability to the end-user" implies evaluation by surgeons, but the number and qualifications of these surgeons are not specified.
4. Adjudication Method for the Test Set
Not applicable for these types of non-clinical tests. Adjudication methods like "2+1" or "3+1" are typically used in clinical studies or image interpretation studies where expert consensus is needed to resolve discrepancies in subjective assessments. Here, the results are based on objective measurements against predefined criteria/standards.
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-powered diagnostic or assistive tool for human readers. Therefore, an MRMC study related to AI assistance would not be relevant.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This device does not involve an algorithm.
7. The Type of Ground Truth Used
The ground truth for most tests is based on:
- Established scientific standards and normative values: e.g., ISO 10993 for biocompatibility, ISO 11135 for sterilization, literature for standard suture repair strength.
- Objective measurements and observations: e.g., cell morphology, concentration of residuals, temperature changes, histological findings, tensile strength measurements, dimensional/visual inspection.
- Comparison to a predicate device: For performance tests, the proposed device's performance is compared directly against the predicate device to demonstrate substantial equivalence or superiority.
8. The Sample Size for the Training Set
Not applicable. This is a physical medical device, not an AI/machine learning model that requires a training set.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this device.
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February 12, 2024
Image /page/0/Picture/1 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 is a blue square with the letters "FDA" in white. To the right of the square, the words "U.S. FOOD & DRUG ADMINISTRATION" are written in blue.
BioCircuit Technologies, Inc. Jack Griffis Scientific Advisor 1819 Peachtree Road NE. Suite 205 Atlanta, Georgia 30309
Re: K233533
Trade/Device Name: NerveTape Regulation Number: 21 CFR 882.5275 Regulation Name: Nerve Cuff Regulatory Class: Class II Product Code: JXI Dated: November 2, 2023 Received: November 2, 2023
Dear Jack Griffis:
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
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2
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Image /page/1/Picture/6 description: The image shows a digital signature. The signature is from Adam D. Pierce. The date of the signature is 2024.02.12, and the time is 17:00:53 -05'00'.
Adam D. Pierce, Ph.D. Assistant Director DHT5A: Division of Neurosurgical. Neurointerventional and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine Devices
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Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K233533
Device Name NerveTape
Indications for Use (Describe)
NerveTape is indicated for the repair of peripheral nerve discontinuities where 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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510(k) Summary
510(k) Number: K233533
February 12, 2024 Date:
This 510(k) summary is being submitted in accordance with the requirements of 21 CFR 807.92.
- A. Submitter: BioCircuit Technologies, Inc. 1819 Peachtree Rd NE, Suite 205 Atlanta, Georgia 30309 (800) 905-2204
- B. Company Contact: Jack Griffis Scientific Advisor (404) 583-6889 (direct) jgriffis@biocircuit.com
- C. Device Information: Trade Name: NerveTape Common Name: Nerve Cuff
- D. Classification: Nerve Cuff 21 CFR §882.5275 (JXI) Class II
- E. Predicate Device: PRIMARY: BioCircuit Technologies, Inc. Nerve Tape™ (K210665) REFERENCE: AxoGuard® Nerve Connector (K162741)
- F. Physical Description:
The proposed BioCircuit Technologies, Inc. NerveTape device is composed of a bioabsorbable, extracellular collagen matrix (small intestinal submucosa, SIS) with integrated microhooks made of a nickel-titanium alloy, commonly referred to as NiTiNOL (identical to the predicate), for mechanical fixation and apposition of nerve ends. The NerveTape is implanted around an injured nerve to provide a scaffold which becomes infiltrated and remodeled by the patient's cells. The device protects the damaged or severed nerve while the nerve heals.
The device is packaged and supplied sterile in a clamshell container inside a sealed pouch. The device is identical to the predicate, except for the SIS substrate manufacturer and the addition of a smaller size. The dimensions of the finished device range from 11mm x 12mm x 22mm. The device is intended for the repair of nerves of diameters ranging from 1.5mm to 7mm.
- G. Indications for Use:
NerveTape is indicated for the repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity.
Comparison to Predicate Device(s):
The BioCircuit Technologies NerveTape device is substantially equivalent with respect to intended use, structure, and technological characteristics to the BioCircuit Technologies device
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cleared under K210665. The devices both have a porcine small intestinal submucosa (SIS) backing (certified to ISO 22442) and operate under the same principle of axonal growth support with an identical form factor (tubular wrap with embedded microhook columns).
The devices differ in the source of the SIS backing substrate and the addition of a smaller sized option (1.5mm nerve compatible), which is equivalent to the original predicate (K162741). The proposed NerveTape device is manufactured with SIS supplied by Smithfield Bioscience, Inc., while the predicate and reference devices are composed of SIS supplied by Cook Biotech, Inc. BioCircuit Technologies, Inc., asserts that any differences from the predicate device do not affect safety or efficacy.
| Parameter | NerveTape(BioCircuit Proposed) | Predicate(BioCircuit) | Reference Predicate(AxoGuard® Nerve Connector) |
|---|---|---|---|
| Manufacturer | BioCircuit Technologies, Inc. | BioCircuit Technologies, Inc. | Cook Biotech Inc. |
| 510(k) Number | K233533 | K162741 | K162741 |
| Product Code | JXI | JXI | JXI |
| Material (wrap) | Porcine small intestinal submucosa:primarily collagen types I, III, IV, and VI(manufactured by Smithfield Bioscience) | Porcine small intestinal submucosa:primarily collagen types I, III, IV, and VI(manufactured by Cook Biotech) | Porcine small intestinal submucosa: primarilycollagen types I, III, IV, and VI (manufacturedby Cook Biotech) |
| Material (hook) | NITINOL (NO CHANGE) | N/A - device is secured to nerves using non-resorbable nylon sutures | |
| Shape | Rectangular wrap (rolls into a hollow tube) (NO CHANGE) | Hollow tube with a slit | |
| Supplied Sterile? | Yes (NO CHANGE) | Yes | |
| Sterilizationmethod | Ethylene Oxide (cycle by Parter SterilizationServices via Bioseal Inc. validated cycle) | Ethylene Oxide (validated cycle by CookBiotech Inc.) | Ethylene Oxide (validated cycle by CookBiotech Inc.) |
| Intended forsingle use? | Yes (NO CHANGE) | Yes | |
| PackagingConfiguration | Clamshell tray in Tyvek-poly pouch with anouter box (packaged by Bioseal Inc.) | Clamshell tray in Tyvek-poly pouch with anouter box (packaged by Cook Biotech) | Clamshell tray in Tyvek pouch with an outerbox (packaged by Cook Biotech) |
| Shelf Life | 18 months (NO CHANGE) | 18 months | |
| Intended use | Intended for peripheral nerve injuries where a gap closure is achieved by flexion of theextremity (NO CHANGE) | Intended for peripheral nerve injuries wherethere is no gap or where a gap closure isachieved by flexion of the extremity. | |
| Dimensions(Wrapped) | 1.5 – 7mm diameter nerve1.2 – 4.5cm width x 1.1 – 2.2cm length(ADDITION OF SMALLER SIZE) | 2 – 7mm diameter nerve1.4 x 4.5cm width x 1.4 - 2.2cm length | 1.5 – 7mm diameter nerve1.5 - 7mm diameter tube x 1 - 1.5 cm length |
| Thickness(Wrapped) | 100-650 μm¹ | 100-750 μm | 100-1000 μm |
| MicrohookHeight | 360 – 550 μm(ADDITION OF SMALLER SIZE USINGSHORTER MICROHOOKS) | 400 - 550 μm | N/A - device is secured to nerves using non-resorbable nylon suture |
| MicrohookColumn Qty | 3 - 8 Columns(ADDITION OF SMALLER SIZE USING 3COLUMNS) | 4-8 Columns | N/A - device is secured to nerves using non-resorbable nylon suture |
Table 1. Table of Substantial Equivalence
4 NOTE: change in thickness is due to the L and L+ sizes of the proposed NerveTape device with only two (2) SIS layers (which is identical to all other sizes). The original (predicate) Nerve Tape device deared under K210665 utilized three (3) SIS layers for the L and L+ sizes and only two (2) SIS layers for all other sizes.
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| Parameter | NerveTape(BioCircuit Proposed) | Predicate(BioCircuit) | Reference Predicate(AxoGuard® Nerve Connector) |
|---|---|---|---|
| Mechanism ofAction | Maintains coaptation via integrated microhooks within the SIS substrate layers, andwrapped around the target site of nerve repair to complete entubulation of the positioned,severed nerve stumps (NO CHANGE) | Maintains coaptation via non-resorbablenylon sutures used to reconnect the ends ofthe nerves while the SIS is positioned aroundthe repair site to complete entubulation of thesutured nerve stumps. |
H. Summary of Non-Clinical Tests:
Product characterization using known standards and / or clinically relevant acceptance criteria was performed on the proposed device. A summary of this testing is provided in Table 2.
| Test | Test Method Summary | Results |
|---|---|---|
| PerformanceVerification: Ease of Use(Simulated Use inCadaver) | Surgeon handling of representative final product; acceptance criteria:product possesses acceptable characteristics for handling, trimming andimplantation | The handling characteristics of the subject deviceare substantially equivalent or superior to thepredicate device based on acceptability to the enduser. All samples met acceptance criteria. |
| PerformanceVerification: MonotonicTensile Strength | Repair strength as assessed via device retention strength on repairedcadaveric nerve in comparison to standard suture repair according tothe literature | The ultimate tensile strength of the proposed devicenerve repairs is substantially equivalent or superiorto the predicate device. All samples met acceptancecriteria. |
| Specification Compliance | Compliance with go/no-go dimensional and visual inspection criteria forall components and assemblies | All samples met acceptance criteria. |
Table 2. Non-Clinical Testing Information
l. Biocompatibility Testing:
Biocompatibility of the predicate device has been established in accordance with ISO 10993-1:2018 – Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process to demonstrate that the device is safe for permanent contact (>30 days) implantation as detailed in Table 3.
Table 3a. Device Biocompatibility Information (all testing performed on sterile product of Iargest size)
| Test | Test Method Summary |
|---|---|
| ANSI/AAMI/ISO 10993-5:2009/(R)2014 – Biologicalevaluation of medical devices –Part 5: Tests for In VitroCytotoxicity | The purpose of the in vitro study was to assess the cytotoxicity potential of extract from the proposeddevice using the Elution test and the mouse cell line L929. The cytotoxic potential of the test article extractwas assessed by the change in morphology of the cell line, which was evaluated microscopically.Based on the criteria of the protocol, the proposed device met the requirements of the test. |
| ANSI/AAMI/ISO 10993-23:2021– Biological evaluation ofmedical devices – Part 23:Tests for Irritation | Intracutaneous reactivity test was conducted with rabbits to determine the potential for the proposeddevice to produce irritation from intradermal injections.Under the conditions of this study, the proposed device met the requirements of the test. The positiveresponse observed in the historical positive control validation study with Hexyl Cinnamic Aldehyde (HCA)validates the test system used in this study. |
| ANSI/AAMI/ISO 10993-10:2021– Biological evaluation ofmedical devices – Part 10:Tests for Skin Sensitization | A guinea pig maximization sensitization test was conducted with guinea pigs to determine the potentialfor the proposed device to invoke a dermal skin sensitization reaction.The study was conducted using a two-stage induction phase and a challenge phase. An emulsion of 50%v/v Freund's Complete Adjuvant (FCA) in saline and sesame oil was used during the intradermal injectioninduction phase.Based on the results of this study, the proposed device met the requirements of the test. |
| ANSI/AAMI/ISO 10993-11:2017– Biological evaluation ofmedical devices – Part 11:Tests for systemic toxicity | An acute systemic toxicity test in mice was conducted to determine the potential for the proposed deviceto produce acute systemic toxicity from a single dose administered by intravenous (IV) and intraperitoneal(IP) injection.Under the conditions of this study, the proposed device met the requirements of the test. |
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| Test | Test Method Summary |
|---|---|
| ANSI/AAMI/ISO 10993-7:2008(R)2012 — BiologicalEvaluation of Medical Devices -Part 7: Ethylene OxideSterilization Residuals | Quantification of sterilant gas residue was performed for the proposed device having been exposed to100% Ethylene oxide (EO). Samples received post sterilization underwent immersion and exhaustiveextractions using purified water and evaluated using gas chromatography. Extractions taken every 24hours post sterilization were pooled and reported for total mg EO and ECH (Ethylene chlorohydrin).Reported values were compared against the ISO standard for acceptable limits at or below therecommended average daily dose for residuals in permanent implants.Under the conditions of this study, the proposed device met the requirements of the test. |
| ANSI/AAMI ST72:2019, USP<161>, USP <85>, EP 2.6.14,and JP 4.01 | A Bacterial Endotoxins Test (BET), or Limulus Amebocyte Lysate (LAL) test, was performed to detect andquantify bacterial endotoxin, a component of the cell wall of Gram-negative bacteria. Standard controlsand a positive product control (PPC) demonstrate a compliant assay. Acceptable detected endotoxins mustnot exceed the maximum allowable limit for permanent implants as per the FDA Guidance DocumentSubmission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for DevicesLabeled as Sterile.Under the conditions of this study, the proposed device met the requirements of the test. |
Table 3b. Decellularized Porcine Small Intestine Submucosa Biocompatibility Information (all testing performed on non-sterile, decellularized porcine small intestine raw material - SIS)
| Test | Test Method Summary |
|---|---|
| ANSI/AAMI/ISO 10993-5:2009/(R)2014 – Biologicalevaluation of medical devices -Part 5: Tests for In VitroCytotoxicity | The purpose of the in vitro study was to assess the cytotoxicity potential of extract from the SIS materialusing the Elution test and the mouse cell line L929. The cytotoxic potential of the test article extract wasassessed by the change in morphology of the cell line, which was evaluated microscopically.Based on the criteria of the protocol, the SIS material met the requirements of the test. |
| The purpose of the in vitro study was to assess the cytotoxicity potential of extract from the SIS materialusing the XTT dye method and the mouse cell line L929. The cell viability and cytotoxic potential of thetest article extracts were determined by quantification of a formazan dye formed in active mitochondriaof living cells. | |
| Based on the criteria of the protocol, the SIS material met the requirements of the test. | |
| ANSI/AAMI/ISO 10993-23:2021 -Biological evaluation of medicaldevices – Part 23: Tests forIrritation | Intracutaneous reactivity test was conducted with rabbits to determine the potential for the SIS materialto produce irritation from intradermal injections. |
| Under the conditions of this study, the SIS material met the requirements of the test and is a non-irritantfor both polar and nonpolar extracts. | |
| ANSI/AAMI/ISO 10993-10:2021– Biological evaluation ofmedical devices – Part 10: Testsfor Skin Sensitization | A guinea pig maximization sensitization test was conducted with guinea pigs to determine the potentialfor the SIS material to invoke a dermal skin sensitization reaction. |
| Based on the results of this study, the SIS material met the requirements of the test and is not consideredto be a contact skin sensitizer. | |
| ANSI/AAMI/ISO 10993-11:2017– Biological evaluation ofmedical devices – Part 11: Testsfor systemic toxicity | An acute systemic toxicity test in mice was conducted to determine the potential for the SIS material toproduce acute systemic toxicity from a single dose administered by intravenous (IV) and intraperitoneal(IP) injection. |
| Under the conditions of this study, the SIS material met the requirements of the test. | |
| ANSI/AAMI/ISO 10993-11:2017– Biological evaluation ofmedical devices – Part 11: Testsfor systemic toxicity | A subacute / subchronic toxicity test in mice was conducted to determine the potential for the SISmaterial to produce systemic toxicity in male and female rats that is likely to arise from repeated exposurevia a dual route approach, intraperitoneal (IP) injection and intravenous (IV) administration, over a periodof at least 14 days. |
| Under the conditions of this study, and based on the toxicological endpoints evaluated, there is nopotential toxicity of the SIS material from repeated exposure via 10 mL/kg/day via intravenously once perday or 5 mL/kg/day via intraperitoneally every three days for both male and female Sprague Dawley rats. | |
| ANSI/AAMI/ISO 10993-11:2017– Biological evaluation ofmedical devices – Part 11: Testsfor systemic toxicity | A material-mediated pyrogenic response test in rabbits was conducted to determine the potential for theSIS material to produce a pyrogenic response due to intravenous exposure. |
| Under the conditions of this study, there were no signs of gross toxicity, adverse clinical effects, orabnormal behavior. None of the animals showed increases in temperature of 0.5℃ or more than theirrespective control temperatures following administration of the SIS material extract. Therefore, and |
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| Test | Test Method Summary |
|---|---|
| based on interpretation of the raw data according to USP-NF<151>, the SIS material met therequirements of the test. | |
| ANSI/AAMI/ISO 10993-3:2014 –Biological evaluation of medicaldevices – Part 3: Tests forGenotoxicity, Carcinogenicity,And Reproductive Toxicity | In Vitro micronucleus testing was conducted to evaluate the potential for extract of the SIS material toinduce micronuclei (clastogenic response) or hypodiploidy (aneugenic response) in cultured ChineseHamster Ovary (CHO) cells in the absence and presence of metabolic activation (S9).Under the conditions of this study, the SIS material extract did not induce micronuclei (via chromosomebreaks and/or loss of whole chromosome(s)) or hypodiploidy (chromosome loss, sub-2n nuclei) incultured CHO cells when tested up to the limit of cytotoxicity (4 hours in the presence of metabolicactivation) and the maximum recommended extract concentration of 0.2 g/mL (4 and 23 hours in theabsence of metabolic activation), and met the requirements of the test. |
| Bacterial mutagenicity testing was conducted to evaluate the potential for extract of the SIS material toinduce gene mutations in bacteria using the Ames assay. Point mutations which involve substitution,addition, or deletion of one or a few DNA base pairs are detected in amino acid-requiring strains ofSalmonella typhimurium (S. typhimurium, ST) and Escherichia coli (E. coli, EC) by their ability tofunctionally reverse mutations. These reverse mutations result in revertant colonies of bacteria withrestored capability to synthesize the essential amino acid.Under the conditions of this study, the SIS material extract did not elicit evidence of bacterialmutagenicity in the Ames assay and met the requirements of the test. | |
| ANSI/AAMI/ISO 10993-6:2016 –Biological evaluation of medicaldevices – Part 6: Tests for LocalEffects After Implantation | Acute intramuscular implantation (4 weeks) of the SIS material was conducted in rabbits and evaluatedhistologically.Under the conditions of this study, the SIS material was well tolerated in comparison to the control articleand met the requirements of the test. |
| Chronic intramuscular implantation (16 weeks) of the SIS material was conducted in rabbits andevaluated histologically.Under the conditions of this study, the SIS material was well tolerated in comparison to the control articleand met the requirements of the test. | |
| Histological Comparisonbetween Native Intestinal Tissueto Decellularized Tissue | Histological evaluation was conducted for the proposed SIS material in comparison to native (non-decellularized) tissue via Hematoxylin & Eosin (H&E) to semi-quantitatively assess the absence of nucleiand cytoplasmic material in the sample, Masson's Trichrome to assess the integrity of the collagennetwork, and immunohistochemistry specific to galactose-α-1,3-galactose (α-gal IHC) to assess the levelof the α-gal antigen present in the ECM.Under the conditions of the tests, the decellularization process of the SIS material was found to haveremoved any microscopic evidence of intact cells that could be detected by light microscopy and left nointact nuclei present in any decellularized section stained by H&E and Masson's Trichrome. In addition, |
J. Sterilization:
The method employed to ensure sterility of the proposed device is provided in Table 4. The sterilization process is identical for the subject and predicate device.
Table 4. Sterilization Information
| Test | Test Method Summary | Results |
|---|---|---|
| Sterilizationvalidation | Validation method in conformance with ISO 11135:2014, Sterilization of healthcare products with ethylene oxide, andAAMI TIR28:2016, Product adoption and process equivalence for ethylene oxide sterilization. | Pass |
K. Animal Studies:
In the animal study conducted, a statistically valid number of rabbits underwent implantation of the proposed NerveTape device or the predicate device on an intact tibial nerve for 4 weeks and
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12 weeks, respectively. The proposed device met all acceptance criteria and was substantially equivalent or superior to the predicate device.
L. Clinical Studies:
No human studies were necessary to prove the safety and efficacy of the device.
M. Conclusion:
No new questions of safety or effectiveness were identified during device testing; therefore, the Nerve Tape device is considered substantially equivalent to the predicate device in terms of safety and effectiveness.
§ 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).