(102 days)
No
The summary describes a physical medical device (a collagen matrix with microhooks) for nerve repair. There is no mention of software, algorithms, or data processing that would suggest the use of AI or ML. The performance studies focus on mechanical properties and biological integration, not algorithmic performance.
Yes
The device is implanted to protect and provide a scaffold for a damaged nerve to heal, which is a therapeutic function.
No
The device is described as an implant used for the repair of peripheral nerve discontinuities, acting as a scaffold to protect and facilitate nerve healing. Its intended use is therapeutic (repair) rather than diagnostic (identifying a condition).
No
The device description clearly states it is composed of physical materials (collagen matrix, microhooks made of NiTiNOL) and is implanted, indicating it is a physical medical device, not software-only.
Based on the provided information, the NerveTape device is not an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use is for the repair of peripheral nerve discontinuities. This is a surgical intervention performed directly on the patient's body.
- Device Description: The device is an implantable material (collagen matrix with microhooks) used to physically support and protect a damaged nerve during healing.
- Mechanism of Action: The device provides a scaffold and mechanical support for nerve regeneration in vivo (within the living organism).
- Lack of Diagnostic Function: The device does not analyze samples (like blood, urine, or tissue) in vitro (outside the body) to provide diagnostic information about a patient's health or condition.
IVD devices are used to examine specimens derived from the human body to provide information for diagnostic, monitoring, or compatibility purposes. The NerveTape device does not fit this description. It is a therapeutic device used for surgical repair.
N/A
Intended Use / Indications for Use
NerveTape is indicated for the repair of peripheral nerve discontinuities where can be achieved by flexion of the extremity.
Product codes
JXI
Device 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
peripheral nerve
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
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)
Study Type: Non-clinical testing: Performance Verification: Ease of Use (Simulated Use in Cadaver), Performance Verification: Monotonic Tensile Strength, Specification Compliance. Biocompatibility testing. Sterilization validation. Animal studies.
Sample Size: Not explicitly stated for all tests. For Biocompatibility testing, "all testing performed on sterile product of largest size" and "all testing performed on non-sterile, decellularized porcine small intestine raw material - SIS". For animal studies, "a statistically valid number of rabbits".
Key results:
- Ease of Use: "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."
- Monotonic Tensile Strength: "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: "All samples met acceptance criteria."
- Biocompatibility: The device and SIS material met the requirements for in vitro cytotoxicity, irritation, skin sensitization, systemic toxicity, ethylene oxide sterilization residuals, and bacterial endotoxins. The SIS material also met requirements for genotoxicity (micronucleus and bacterial mutagenicity) and local effects after implantation (acute and chronic intramuscular implantation). Histological comparison showed effective decellularization.
- Sterilization: Validation met ISO 11135:2014 and AAMI TIR28:2016, resulting in "Pass".
- Animal Studies: "The proposed device met all acceptance criteria and was substantially equivalent or superior to the predicate device."
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s)
BioCircuit Technologies, Inc. Nerve Tape™ (K210665)
Reference Device(s)
AxoGuard® Nerve Connector (K162741)
Predetermined Change Control Plan (PCCP) - All Relevant Information
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).
0
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).
1
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
2
Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
3
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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
4
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
5
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: primarily
collagen types I, III, IV, and VI (manufactured
by 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 |
| Sterilization
method | Ethylene Oxide (cycle by Parter Sterilization
Services via Bioseal Inc. validated cycle) | Ethylene Oxide (validated cycle by Cook
Biotech Inc.) | Ethylene Oxide (validated cycle by Cook
Biotech Inc.) |
| Intended for
single use? | Yes (NO CHANGE) | | Yes |
| Packaging
Configuration | Clamshell tray in Tyvek-poly pouch with an
outer box (packaged by Bioseal Inc.) | Clamshell tray in Tyvek-poly pouch with an
outer box (packaged by Cook Biotech) | Clamshell tray in Tyvek pouch with an outer
box (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 the
extremity (NO CHANGE) | | Intended for peripheral nerve injuries where
there is no gap or where a gap closure is
achieved by flexion of the extremity. |
| Dimensions
(Wrapped) | 1.5 – 7mm diameter nerve
1.2 – 4.5cm width x 1.1 – 2.2cm length
(ADDITION OF SMALLER SIZE) | 2 – 7mm diameter nerve
1.4 x 4.5cm width x 1.4 - 2.2cm length | 1.5 – 7mm diameter nerve
1.5 - 7mm diameter tube x 1 - 1.5 cm length |
| Thickness
(Wrapped) | 100-650 μm¹ | 100-750 μm | 100-1000 μm |
| Microhook
Height | 360 – 550 μm
(ADDITION OF SMALLER SIZE USING
SHORTER MICROHOOKS) | 400 - 550 μm | N/A - device is secured to nerves using non-
resorbable nylon suture |
| Microhook
Column Qty | 3 - 8 Columns
(ADDITION OF SMALLER SIZE USING 3
COLUMNS) | 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.
6
| Parameter | NerveTape
(BioCircuit Proposed) | Predicate
(BioCircuit) | Reference Predicate
(AxoGuard® Nerve Connector) |
|------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Mechanism of
Action | Maintains coaptation via integrated microhooks within the SIS substrate layers, and
wrapped around the target site of nerve repair to complete entubulation of the positioned,
severed nerve stumps (NO CHANGE) | | Maintains coaptation via non-resorbable
nylon sutures used to reconnect the ends of
the nerves while the SIS is positioned around
the repair site to complete entubulation of the
sutured 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 |
|---|---|---|
| Performance | ||
| Verification: Ease of Use | ||
| (Simulated Use in | ||
| Cadaver) | Surgeon handling of representative final product; acceptance criteria: | |
| 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. |
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 – Biological | |
| evaluation of medical devices – | |
| Part 5: Tests for In Vitro | |
| Cytotoxicity | The purpose of the in vitro study was to assess the cytotoxicity potential of extract from the proposed |
| device using the Elution test and the mouse cell line L929. The cytotoxic potential of the test article extract | |
| was 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 of | |
| medical devices – Part 23: | |
| Tests for Irritation | Intracutaneous reactivity test was conducted with rabbits to determine the potential for the proposed |
| device to produce irritation from intradermal injections. | |
| Under the conditions of this study, the proposed device met the requirements of the test. The positive | |
| response 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 of | |
| medical devices – Part 10: | |
| Tests for Skin Sensitization | A guinea pig maximization sensitization test was conducted with guinea pigs to determine the potential |
| for 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 injection | |
| induction 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 of | |
| medical devices – Part 11: | |
| Tests for systemic toxicity | An acute systemic toxicity test in mice was conducted to determine the potential for the proposed device |
| to 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. |
7
| Test | Test Method Summary |
|---|---|
| ANSI/AAMI/ISO 10993- | |
| 7:2008(R)2012 — Biological | |
| Evaluation of Medical Devices - | |
| Part 7: Ethylene Oxide | |
| Sterilization Residuals | Quantification of sterilant gas residue was performed for the proposed device having been exposed to |
| 100% Ethylene oxide (EO). Samples received post sterilization underwent immersion and exhaustive | |
| extractions using purified water and evaluated using gas chromatography. Extractions taken every 24 | |
| hours 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 the | |
| recommended 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 | |
| , USP , EP 2.6.14, | |
| and JP 4.01 | A Bacterial Endotoxins Test (BET), or Limulus Amebocyte Lysate (LAL) test, was performed to detect and |
| quantify bacterial endotoxin, a component of the cell wall of Gram-negative bacteria. Standard controls | |
| and a positive product control (PPC) demonstrate a compliant assay. Acceptable detected endotoxins must | |
| not exceed the maximum allowable limit for permanent implants as per the FDA Guidance Document | |
| Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices | |
| Labeled 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 – Biological | |
| evaluation of medical devices - | |
| Part 5: Tests for In Vitro | |
| Cytotoxicity | The purpose of the in vitro study was to assess the cytotoxicity potential of extract from the SIS material |
| using the Elution test and the mouse cell line L929. The cytotoxic potential of the test article extract was | |
| assessed 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 material | |
| using the XTT dye method and the mouse cell line L929. The cell viability and cytotoxic potential of the | |
| test article extracts were determined by quantification of a formazan dye formed in active mitochondria | |
| of 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 medical | |
| devices – Part 23: Tests for | |
| Irritation | Intracutaneous reactivity test was conducted with rabbits to determine the potential for the SIS material |
| to produce irritation from intradermal injections. | |
| Under the conditions of this study, the SIS material met the requirements of the test and is a non-irritant | |
| for both polar and nonpolar extracts. | |
| ANSI/AAMI/ISO 10993-10:2021 | |
| – Biological evaluation of | |
| medical devices – Part 10: Tests | |
| for Skin Sensitization | A guinea pig maximization sensitization test was conducted with guinea pigs to determine the potential |
| for 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 considered | |
| to be a contact skin sensitizer. | |
| ANSI/AAMI/ISO 10993-11:2017 | |
| – Biological evaluation of | |
| medical devices – Part 11: Tests | |
| for systemic toxicity | An acute systemic toxicity test in mice was conducted to determine the potential for the SIS material to |
| produce 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 of | |
| medical devices – Part 11: Tests | |
| for systemic toxicity | A subacute / subchronic toxicity test in mice was conducted to determine the potential for the SIS |
| material to produce systemic toxicity in male and female rats that is likely to arise from repeated exposure | |
| via a dual route approach, intraperitoneal (IP) injection and intravenous (IV) administration, over a period | |
| of at least 14 days. | |
| Under the conditions of this study, and based on the toxicological endpoints evaluated, there is no | |
| potential toxicity of the SIS material from repeated exposure via 10 mL/kg/day via intravenously once per | |
| day 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 of | |
| medical devices – Part 11: Tests | |
| for systemic toxicity | A material-mediated pyrogenic response test in rabbits was conducted to determine the potential for the |
| SIS 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, or | |
| abnormal behavior. None of the animals showed increases in temperature of 0.5℃ or more than their | |
| respective control temperatures following administration of the SIS material extract. Therefore, and |
8
| Test | Test Method Summary |
|---|---|
| based on interpretation of the raw data according to USP-NF, the SIS material met the | |
| requirements of the test. | |
| ANSI/AAMI/ISO 10993-3:2014 – | |
| Biological evaluation of medical | |
| devices – Part 3: Tests for | |
| Genotoxicity, Carcinogenicity, | |
| And Reproductive Toxicity | In Vitro micronucleus testing was conducted to evaluate the potential for extract of the SIS material to |
| induce micronuclei (clastogenic response) or hypodiploidy (aneugenic response) in cultured Chinese | |
| Hamster 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 chromosome | |
| breaks and/or loss of whole chromosome(s)) or hypodiploidy (chromosome loss, sub-2n nuclei) in | |
| cultured CHO cells when tested up to the limit of cytotoxicity (4 hours in the presence of metabolic | |
| activation) and the maximum recommended extract concentration of 0.2 g/mL (4 and 23 hours in the | |
| absence 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 to | |
| induce 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 of | |
| Salmonella typhimurium (S. typhimurium, ST) and Escherichia coli (E. coli, EC) by their ability to | |
| functionally reverse mutations. These reverse mutations result in revertant colonies of bacteria with | |
| restored capability to synthesize the essential amino acid. | |
| Under the conditions of this study, the SIS material extract did not elicit evidence of bacterial | |
| mutagenicity in the Ames assay and met the requirements of the test. | |
| ANSI/AAMI/ISO 10993-6:2016 – | |
| Biological evaluation of medical | |
| devices – Part 6: Tests for Local | |
| Effects After Implantation | Acute intramuscular implantation (4 weeks) of the SIS material was conducted in rabbits and evaluated |
| histologically. | |
| Under the conditions of this study, the SIS material was well tolerated in comparison to the control article | |
| and met the requirements of the test. | |
| Chronic intramuscular implantation (16 weeks) of the SIS material was conducted in rabbits and | |
| evaluated histologically. | |
| Under the conditions of this study, the SIS material was well tolerated in comparison to the control article | |
| and met the requirements of the test. | |
| Histological Comparison | |
| between Native Intestinal Tissue | |
| to 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 nuclei | |
| and cytoplasmic material in the sample, Masson's Trichrome to assess the integrity of the collagen | |
| network, and immunohistochemistry specific to galactose-α-1,3-galactose (α-gal IHC) to assess the level | |
| of the α-gal antigen present in the ECM. | |
| Under the conditions of the tests, the decellularization process of the SIS material was found to have | |
| removed any microscopic evidence of intact cells that could be detected by light microscopy and left no | |
| intact 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 |
|---|---|---|
| Sterilization | ||
| validation | Validation method in conformance with ISO 11135:2014, Sterilization of healthcare products with ethylene oxide, and | |
| AAMI 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
9
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.