Remplir™ is a sterile, implantable, biocompatible, resorbable, collagen membrane intended for use in the management of peripheral nerve injuries in which there has been no substantial loss of nerve tissue. Remplir™ is a single-ply sheet of porcine-derived, non-crosslinked collagen. It presents as a soft and pliable, white to off-white membrane with distinct smooth and rough surfaces.

The primary aim of surgical repair is to re-establish nerve continuity so that regenerating axons are guided into the distal nerve stump with minimal loss of nerve fibres at the repair site. Remplir™ is designed to protect the injured nerve. The device can be cut to the desired size and wrapped around the injured nerve in either its wet or dry form. It is wrapped around the site of nerve repair, intended to provide a favourable environment for nerve regeneration and prevent ingrowth of connective tissue.

Remplir™ is supplied as a single device in a double PETG/Tyvek blister pack in a labelled cardboard box. Remplir™ is available in 4 size variants for the convenience of clinicians (15 mm x 20 mm, 20 mm x 30 mm, 30 mm x 40 mm, 40 mm x 50 mm.). All size variants are identical in composition and function.

AI/ML Overview

The Remplir Nerve Cuff is indicated for the management of peripheral nerve injuries where there has been no substantial loss of nerve tissue. The device is a sterile, implantable, biocompatible, resorbable, collagen membrane derived from porcine tissue.

Here's the breakdown of the acceptance criteria and the study that proves the device meets them:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the results of the performance testing which successfully met specifications, demonstrating substantial equivalence to the predicate device.

Acceptance Criteria (Implied)	Reported Device Performance
Suturability: Sufficient suture retention strength for intended use.	Test completed and met specification. Device has sufficient suture retention strength for its intended use, comparable to the predicate.
Tensile Strength: Suitable for intended use.	Test completed and met specification. Tensile strength is suitable for intended use, comparable to the predicate device.
Biocompatibility: Non-cytotoxic, non-irritating, non-sensitizing, non-toxic, non-genotoxic, non-mutagenic, and non-pyrogenic.	Biocompatibility studies demonstrated Remplir™ to be non-cytotoxic, non-irritating, non-sensitizing, non-toxic, non-genotoxic, non-mutagenic, and non-pyrogenic.
Sterilization: Sterility Assurance Level (SAL) of 10⁻⁶.	Testing completed and met specifications (ISO 11137).
Endotoxin: Meets specified limits.	Testing completed and met specification (USP <85> and AAMI ST72, specifically USP <161>).
In vivo Performance (Nerve Repair): Similar tissue response and nerve changes compared to predicate control material when surgically implanted around a transected nerve. Minimal or no reaction during nerve regeneration.	At all time points (4, 12, and 24 weeks) in the rat transected sciatic nerve model, changes observed in the nerve were similar between the device and predicate control material and were typical of nerve transection. At all time points, the device elicited no or minimal reaction compared to the predicate control.

2. Sample Size Used for the Test Set and Data Provenance

The primary in-vivo performance study used a rat transected sciatic nerve model. While the exact number of rats (sample size) is not explicitly stated, the study measured data at 4, 12, and 24 weeks. The provenance of this data is a pre-clinical animal study, typically conducted in-house by the manufacturer or a contract research organization. The country of origin for the data is not specified in the document.

The other performance tests (Suturability, Tensile Strength, Biocompatibility, Sterilization, Endotoxin) are benchtop or laboratory tests, and their "sample size" would refer to the number of device units tested for each specific parameter. These details are not provided in this summary.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

For the animal study ("Rat transected sciatic nerve model"), the "ground truth" would likely be established through histological examination and evaluation of nerve regeneration and tissue response. The document does not specify the number of experts or their qualifications for interpreting these results. Such expertise would typically involve veterinary pathologists or histologists with experience in nerve tissue assessment.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the interpretation of the animal study results. It implies that the "changes observed" and "reaction" were assessed and compared.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is typically associated with diagnostic imaging devices or AI-assisted diagnostic tools where the performance of human readers with and without AI assistance is evaluated. The Remplir Nerve Cuff is an implantable medical device, and its performance is assessed through bench testing and in-vivo animal studies, not through human reader interpretation. No effect size of human readers improving with AI vs. without AI assistance is applicable or reported.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

No, a standalone (algorithm only) performance study was not done. Remplir is a physical medical device, not a software algorithm. Therefore, the concept of "standalone performance" for an algorithm without human-in-the-loop is not applicable here.

7. The Type of Ground Truth Used

For the in-vivo animal study, the ground truth was histopathological observation and assessment of the nerve tissue and surrounding environment at different time points (4, 12, and 24 weeks) after implantation. This involves microscopic examination of stained tissue sections to evaluate nerve regeneration, inflammation, and integration of the device. The comparison against a "marketed predicate control material" served as the reference for determining acceptable performance.

For the benchtop tests (Suturability, Tensile Strength, Biocompatibility, Sterilization, Endotoxin), the ground truth is established by pre-defined specifications and validated testing methodologies (e.g., ISO standards, USP monographs) which are considered objective and measurable.

8. The Sample Size for the Training Set

The concept of a "training set" is generally applicable to machine learning algorithms or AI models. Since Remplir™ is a physical medical device and not an AI/ML product, there is no training set in the context of machine learning. The device development would involve design, material selection, and manufacturing process optimization, which are not typically referred to as "training" in this sense.

9. How the Ground Truth for the Training Set Was Established

As there is no "training set" for this physical medical device, this question is not applicable.

Summary

FDA 510(k) Clearance Letter - Remplir Nerve Cuff

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U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.07.05

April 2, 2025

Orthocell Ltd.
℅ Kristin Zielinski Duggan
Partner, Hogan Lovells US LLP
Columbia Square, 555 Thirteenth Street, NW
Washington, District of Columbia 20004

Re: K243889
Trade/Device Name: Remplir (ON-152, 15 x 20 mm); Remplir (ON-203, 20 x 30 mm); Remplir (ON-304, 30 x 40 mm); Remplir (ON-405, 40 x 50 mm)
Regulation Number: 21 CFR 882.5275
Regulation Name: Nerve Cuff
Regulatory Class: Class II
Product Code: JXI
Dated: December 18, 2024
Received: December 18, 2024

Dear Kristin Zielinski Duggan:

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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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 QS 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 (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-reporting-combination-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.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

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-devices/medical-device-safety/medical-device-reporting-mdr-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/medical-devices/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-devices/device-advice-comprehensive-regulatory-assistance/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).

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Sincerely,

Adam D. Pierce, Ph.D.
Assistant Director
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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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

Submission Number (if known): K243889

Device Name:

Remplir (ON-152, 15 x 20 mm)
Remplir (ON-203, 20 x 30 mm)
Remplir (ON-304, 30 x 40 mm)
Remplir (ON-405, 40 x 50 mm)

Indications for Use (Describe):
Remplir 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)

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:

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510(k) Summary

Remplir™

SUBMITTER

Field	Details
Name	Orthocell Ltd
Address	Building 191, Murdoch UniversitySouth Street, Murdoch WA 6150AUSTRALIA
Contact Person	Kelly Hunter
Phone	+ 61 8 9360 6268
Date	April 2, 2025

DEVICE

Field	Details
Trade Name	Remplir™
Common Name	Nerve Wrap
Classification Name	Nerve Cuff (21 CFR 882.5275)
Regulatory Class	Class II
Product Code	JXI

PREDICATE DEVICE

Remplir™ is substantially equivalent in function and intended use to following predicate device:

Field	Details
Trade Name	NeuraWrap™
Classification Name	K041620

DEVICE DESCRIPTION

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INDICATIONS FOR USE

Remplir™ is indicated for the management of peripheral nerve injuries in which there has been no substantial loss of nerve tissue.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

The subject device (Remplir™) is substantially equivalent in function, intended use/indications for use and technological characteristics of the predicate device (NeuraWrap™). The table below summarizes the comparison between the predicate device and Remplir™.

Device Comparison Table: Remplir™ and NeuraWrap™

Device	Remplir™ (Subject device)	NeuraWrap™ (Predicate, K041620)
Indications for use	Remplir™ is indicated for the management of peripheral nerve injuries in which there has been no substantial loss of nerve tissue.	NeuraWrap™ is indicated for the management of peripheral nerve injuries in which there has been no substantial loss of nerve tissue.
Configuration / Presentation	Presents as a flexible, dry, white sheet.Rollable sheet	Presents as a flexible, dry, white sheetHollow Tube
Composition	Type 1 collagen, porcine	Type 1 collagen, bovine
Technological characteristics	ResorbableSuturableAbsorbentRetains mechanical strength when wet	ResorbableSuturableAbsorbentRetains mechanical strength when wet
Sterile/Single Use	Sterile; single use	Sterile; single use
Packaging	Double PETG trays with Tyvek® seals	Double PETG trays with Tyvek® seals
Sterilization	Gamma Irradiation	Ethylene Oxide (EO)

PERFORMANCE DATA

The following performance data was performed on the Remplir™ nerve wrap device.

Purpose of Test	Test Method Summary	Results
Suturability	The suturability of Remplir™ was determined by performing suture pull out testing.	Test was completed and met specification. Like the predicate, the device has sufficient suture retention strength for its intended use.
Tensile Strength	Tensile strength was determined by placing the device between two grips and measuring the separation force required to reach device failure.	Test was completed and met specification. Like the predicate device, the tensile strength is suitable for intended use.

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Purpose of Test	Test Method Summary	Results
Biocompatibility	Biocompatibility testing was conducted in accordance with the requirements of ISO 10993	Biocompatibility studies have demonstrated Remplir™ to be non-cytotoxic, non-irritating, non-sensitizing, non-toxic, non-genotoxic, non-mutagenic, and non-pyrogenic
Sterilisation	The sterilization process was validated to achieve a sterility assurance level (SAL) of 10⁻⁶ per ISO 11137	Testing was completed and met specifications.
Endotoxin	The bacterial endotoxin validation testing was conducted per USP <85> and AAMI ST72	Testing was completed and met specification (USP<161>)
Rat transected sciatic nerve model	The device was surgically implanted around the transected sciatic nerve of the rat and compared to nerves wrapped with marketed predicate control material. Data were collected at 4, 12 and 24 weeks.	At all time points the changes observed in the nerve were similar between device and predicate control material and were typical of changes in a nerve after transection. At all time points the device was considered to elicit no or minimal reaction in comparison to the predicate control.

CONCLUSION

The intended use/indications for use, principles of operation, and technological characteristics of Remplir™ are substantially equivalent to the predicate device NeuraWrap™ (K041620). The safety, performance and effectiveness of Remplir™ for its intended use is demonstrated by bench and animal studies. Based on the evidence provided, the subject device, Remplir™ is substantially equivalent to the legally marketed predicate device, NeuraWrap™.

Regulation Number and Section

§ 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).