(90 days)
VersaWrap Nerve Protector is indicated for the management of peripheral nerve injuries in which there has been no substantial loss of nerve tissue.
VersaWrap Nerve Protector (VersaWrap) is designed to function as an interface between an injured nerve and surrounding tissues and is indicated for use in peripheral nerve injuries where there is no significant loss of nerve tissue. VersaWrap Nerve Protector is a thin, flexible implant, designed to be a non-constricting gelatinous interface encasing peripheral nerves and the neural environment; that starts to absorb after implant. VersaWrap Nerve Protector is designed to be flexible and conformable for placement around a peripheral nerve
The provided text describes non-clinical tests and an animal study for the VersaWrap Nerve Protector. Here's a breakdown of the requested information based on the provided input:
1. A table of acceptance criteria and the reported device performance
| Acceptance Criteria Category | Specific Test/Purpose | Acceptance Criteria Summary | Reported Device Performance |
|---|---|---|---|
| Non-Clinical Tests | Dimensional & Visual Inspection | Direct measurement of mass, lengths, width, thickness with micrometers, calipers, pH meter or balance; and visual inspection. | Dimensional analysis was completed to verify the dimensions and visual characteristics and met specifications. |
| Pliability/Tissue Conformance and Adherence | The device is placed on a simulated model and graded for visual conformance and adherence. | Visual inspection was conducted and met specifications. | |
| Swelling | Direct measurement of the device (with micrometers, calipers) when exposed to fluid. | Dimensional analysis was completed and met specifications. | |
| Strength/Puncture | Direct measurement of the device strength/puncture when measured with a probe. | Testing was completed and met specifications. | |
| Pouch Seal Integrity/Sterile Barrier | The integrity of the pouch was verified with a visual inspection, peel tester, and burst tester. | Testing was completed and met specifications. | |
| Sterilization | The e-beam sterilization process was validated to achieve a sterility assurance level (SAL) of 10-6 per ISO 11137. | Testing was completed and met specifications. | |
| Bacterial Endotoxin Validation | The bacterial endotoxin validation testing was conducted per USP <85> Bacterial Endotoxins and Ph.Eur. Chpt 2.6.14. | Testing was completed and met specification. | |
| Cytotoxicity | The device was evaluated for potential cytotoxic effects using an in vitro mammalian cell culture test, following ISO 10993-5 guidelines. | The test extract showed no evidence of causing cell lysis or toxicity. | |
| Sensitization | The device was evaluated for the potential to cause delayed dermal contact sensitization in a guinea pig maximization test, based on ISO 10993-10. | The test article showed no evidence of causing delayed contact sensitization. | |
| Irritation | The device was evaluated for the potential to cause irritation following intracutaneous injection, based on ISO 10993-10. | There was no evidence of significant irritation from the extracts injected intracutaneously. | |
| Acute Systemic Toxicity | The device was evaluated for acute systemic toxicity, based on ISO 10993-11. | The sesame oil test article extracts and the sodium chloride test article extracts injected met the passing requirements of the test. | |
| Pyrogenicity | The device was evaluated for material mediated pyrogenicity in the rabbit. | The total rise of temperatures during the observation period was within acceptable limits (implied by "Testing was completed and met specifications" below). | |
| Genotoxicity | The device was evaluated for mutagenic potential, mutagenic changes, and to produce cytogenetic damage. | Extract did not cause cytogenetic damage/micronuclei formation. Extracts were well within the limits defined for a negative response and the test article is considered non-mutagenic. | |
| Subchronic Toxicity | The device was surgically implanted in the subcutaneous tissue of the rat to evaluate potential systemic toxicity and local tissue response at the implantation sites. | No evidence of systemic toxicity following subcutaneous implantation. Microscopically, the test article was classified as a non-irritant. | |
| Muscle Implantation | The study assessed local tissue effects and absorption profile following implantation in muscle tissue in at multiple timepoints. | At long term timepoints the device was considered to be a non-irritant and a slight irritant at earlier weeks following implantation when compared to the control. Microscopic evaluation demonstrated the device is bioresorbing as expected. | |
| Neurotoxicity Assessment | A risk analysis was conducted to determine any neurotoxicity risk to the patient. | An analysis was conducted to determine any neurotoxicity risk to the patient (implied satisfactory outcome given overall conclusion). | |
| Animal Study | Performance/Safety | Comparable safety and performance to predicate device, no significant events, no apparent difference in character or severity of reactivity to test or predicate implant, no microscopic changes in the nerve at any interval for either test or Integra implants, similar microscopic appearance of nerve and surrounding tissue for control and VersaWrap. | VersaWrap animals and the predicate control animals demonstrated equivalent safety and equivalent performance results; there were no significant events reported in any group. Histopathological evaluations showed no apparent difference in the character or severity of the reactivity, and no microscopic changes in the nerve. |
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: The document states the "sample size was selected to be large enough to show consistent results and to be able to compare the test, control, and untreated groups" for the animal study. However, a specific numerical sample size is not explicitly provided for the animal study (e.g., "N=X rats"). For non-clinical tests, sample sizes are implied by "testing was completed" but not detailed (e.g., number of pouches for seal integrity, number of samples for cytotoxic evaluation).
- Data Provenance:
- Country of Origin: Not specified.
- Retrospective or Prospective: The animal study appears to be prospective as it involved conducting the study on "multiple injury types for subject device, predicate control device, and untreated groups" with data collected at "an early period, a mid-term period; and a late period." The non-clinical tests are also inherently prospective as they are performed on the device.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- The document does not provide information on the number of experts or their qualifications used to establish ground truth for the animal study or any other test. It mentions "Histopathological evaluations were performed," which implies expert analysis, but details are lacking.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- The document does not specify any adjudication method for the test set, whether for the animal study or non-clinical tests.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No, an MRMC comparative effectiveness study was not done. This device is a physical nerve protector and not an AI-assisted diagnostic tool. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
- No, a standalone algorithm-only performance study was not done. This device is a physical medical implant, not an algorithm or software.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- For the animal study, the ground truth appears to be based on pathology/histopathology ("Histopathological evaluations were performed to assess local and systemic tissue effects...There were no microscopic changes in the nerve...") and physiological/observational outcomes data ("motor and sensory neurological assessments were conducted...no significant events reported").
- For non-clinical tests, the "ground truth" is typically defined by pre-defined specifications and validated test methods (e.g., ISO standards for biocompatibility, direct measurements for dimensional analysis).
8. The sample size for the training set
- This device is not an AI/ML model, so there is no concept of a "training set" as described in the context of AI.
9. How the ground truth for the training set was established
- As there is no training set for an AI/ML model, this question is not applicable.
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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 consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
September 14, 2020
Alafair Biosciences, Inc. % Angela Mallery Regulatory Consultant NAMSA 400 Highway 169 South, Suite 500 Minneapolis, Minnesota 55426
Re: K201631
Trade/Device Name: VersaWrap Nerve Protector Regulation Number: 21 CFR 882.5275 Regulation Name: Nerve Cuff Regulatory Class: Class II Product Code: JXI Dated: June 12, 2020 Received: June 16, 2020
Dear Angela Mallery:
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
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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 devices or postmarketing safety reporting (21 CFR 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 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
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/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).
Sincerely,
Adam Pierce, Ph.D. Assistant Director (Acting) 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
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Indications for Use
510(k) Number (if known) K201631
Device Name VersaWrap Nerve Protector
Indications for Use (Describe)
VersaWrap Nerve Protector is indicated for the management of peripheral nerve injuries in which there has been no substantial loss of nerve tissue.
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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| 510(k) SummaryVersaWrap Nerve Protector | ||||
|---|---|---|---|---|
| K201631 | ||||
| Submitted by: | Alafair Biosciences, Inc.6101 W Courtyard DriveSte. 2-225Austin, TX 78730800.206.5586; info@alafairbiosciences.com | |||
| Date Prepared: | September 8, 2020 | |||
| Contact: | Ben Walthall, Ph.D.Chief Regulatory Officer800.206.5586; info@alafairbiosciences.com | |||
| Product Name | VersaWrap Nerve Protector | |||
| Common Name | Cuff, Nerve | |||
| Classification number | 21 CFR 882.5275 | |||
| Product Code | JXI | |||
| Primary Predicate: | Integra NeuraWrap Nerve Protector K041620 | |||
| Reference Device: | Alafair VersaWrap Tendon Protector K200311 | |||
| Device Description: | VersaWrap Nerve Protector (VersaWrap) is designed to function as an interface between aninjured nerve and surrounding tissues and is indicated for use in peripheral nerve injurieswhere there is no significant loss of nerve tissue.VersaWrap Nerve Protector is a thin, flexible implant, designed to be a non-constrictinggelatinous interface encasing peripheral nerves and the neural environment; that starts toabsorb after implant.VersaWrap Nerve Protector is designed to be flexible and conformable for placementaround a peripheral nerve | |||
| Indications for Use: | VersaWrap Nerve Protector is indicated for the management of peripheral nerve injuries inwhich there has been no substantial loss of nerve tissue. | |||
| Functional and SafetyTesting: | Biocompatibility studies demonstrated the Nerve Protector is non-cytotoxic, non-pyrogenic,non-irritating, non-sensitizing, non-toxic, and non-genotoxic. Animal studies demonstratedthe device performed as labeled. | |||
| ComparativeTechnologyCharacteristics: | ParameterDevice name | DeviceVersaWrap | Predicate DeviceNeuraWrap | Reference DeviceVersaWrap |
| CompanyName | Alafair Biosciences | Integra Lifesciences | Alafair Biosciences | |
| 510(k) # | K201631 | K041620 | K200311 | |
| Material | Calcium alginate andhyaluronic acid | Type 1 bovinecollagen andchondroitin-6-sulfate | Calcium alginate andhyaluronic acid | |
| Intended Use | designed to be aninterface between theinjured area and thesurrounding tissue | designed to be aninterface between theinjured area and thesurrounding tissue | designed to be aninterface between theinjured area and thesurrounding tissue | |
| Packaging | Double Pouch | Double Pouch | Double Pouch | |
| PhysicianStructure | Sheet | Tube | Sheet | |
| SterilizationMethod | eBeam | EO | eBeam | |
| Testing was conducted. The specific conclusions drawn from the testing is that thetesting demonstrates the proposed device is as safe, as effective, and performs as wellas or better than the legally marketed predicate device. | ||||
| Test/Purpose | Test Method Summary | Discussion of results | ||
| Non-Clinical TestsPerformed: | Dimensional andvisual inspection | Direct measurement of the mass,lengths, width, thickness withmicrometers, calipers, pH meteror balance; and visual inspection. | Dimensional analysiswas completed to verifythe dimensions andvisual characteristics andmet specifications; | |
| Pliability/ Tissueconformance andadherence | The device is placed on asimulated model and graded forvisual conformance andadherence. | Visual inspection wasconducted and metspecifications. | ||
| Swelling | Direct measurement of the device(with micrometers, calipers) whenexposed to fluid. | Dimensional analysiswas completed and metspecifications. | ||
| Strength/Puncture | Direct measurement of the devicestrength/puncture when measuredwith a probe. | Testing was completedand met specifications. | ||
| Pouch SealIntegrity/SterileBarrier | The integrity of the pouch wasverified with a visual inspection,peel tester, and burst tester. | Testing was completedand met specifications. | ||
| Sterilization | The e-beam sterilization processwas validated to achieve a sterilityassurance level (SAL) of 10-6 perISO 11137 | Testing was completedand met specifications. | ||
| Bacterialendotoxinvalidation | The bacterial endotoxin validationtesting was conducted per USP<85> Bacterial Endotoxins andPh.Eur. Chpt 2.6.14 | Testing was completedand met specification | ||
| Cytotoxicity | The device was evaluated forpotential cytotoxic effects using anin vitro mammalian cell culture test.This study was conducted followingthe guidelines of ISO 10993-5 | The test extract showed noevidence of causing celllysis or toxicity. | ||
| Sensitization | The device was evaluated for thepotential to cause delayed dermalcontact sensitization in a guinea pigmaximization test. This study wasconducted based on therequirements of ISO 10993-10 | The test article showed noevidence of causing delayedcontact sensitization. | ||
| Irritation | The device was evaluated for thepotential to cause irritationfollowing intracutaneous injection.This study was conducted based onISO 10993-10 | There was no evidence ofsignificant irritation fromthe extracts injectedintracutaneously. | ||
| Acute systemictoxicity | The device was evaluated for acutesystemic toxicity. This study wasconducted based on ISO 10993-11. | The sesame oil test articleextracts and the sodiumchloride test article extractsinjected met the passingrequirements of the test. | ||
| Pyrogenicity | The device was evaluated formaterial mediated pyrogenicity inthe rabbit. The test was conducted | The total rise oftemperatures during theobservation period was |
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| Genotoxicity | The device was evaluated formutagenic potential, mutagenicchanges, and to produce cytogeneticdamage | Extract did not causecytogenetic damage/micronuclei formation.Extracts were well withinthe limits defined for anegative response and thetest article is considerednon-mutagenic andconsidered to be non-mutagenic |
|---|---|---|
| Subchronictoxicity | The device was surgicallyimplanted in the subcutaneoustissue of the rat to evaluate potentialsystemic toxicity and local tissueresponse at the implantation sites | No evidence of systemictoxicity followingsubcutaneous implantation.Microscopically, the testarticle was classified as anon-irritant. |
| Muscleimplantation | The purpose of this study was toassess the local tissue effects andabsorption profile followingimplantation in muscle tissue in atmultiple timepoints. | At long term timepoints thedevice was considered to bea non-irritant and a slightirritant at earlier weeksfollowing implantationwhen compared to thecontrol. At the study mid-point, microscopicevaluation demonstrated thedevice is bioresorbing asexpected. This variable andslight irritation is expectedfor a device undergoingabsorption. |
| Neurotoxicityassessment | A risk analysis was conducted | An analysis was conductedto determine anyneurotoxicity risk to thepatient |
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| Animal Study | The animal study was conducted on multiple injury types forsubject device, predicate control device, and untreated groups.Nerve defects were comparable to the clinical use of the device.Data was collected at an early period, a mid-term period; and alate period.The rat is often used in nerve injury models and is suggested inthe ISO standards and Organisation for Economic Co-operationand Development guidelines as an acceptable animal model forevaluating the local tissue response of various articles; and thesample size was selected to be large enough to show consistentresults and to be able to compare the test, control, and untreatedgroups.As recommended by FDA, motor and sensory neurologicalassessments were conducted prior to surgery, and throughout thestudy. VersaWrap animals and the predicate control animalsdemonstrated equivalent safety and equivalent performanceresults; there were no significant events reported in any group.Histopathological evaluations were performed to assess local andsystemic tissue effects specific to the test and predicate controlarticles. Overall, there was no apparent difference in the characteror severity of the reactivity to the test or predicate implant. Therewere no microscopic changes in the nerve at any interval foreither test or Integra implants; the microscopic appearance of thenerve and surrounding tissue for both the control and VersaWrapwere similar. |
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| -------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Conclusion | Based on the results of animal studies, prior in vitro product characterization studies, in vitro and in vivo biocompatibility and performance studies, we conclude the device is as safe as, and substantially equivalent to its predicate devices. |
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§ 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).