REBOSSIS is a bone void filler intended for use in bony voids or gaps that are not intrinsic to the stability of the bony structure. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. REBOSSIS is indicated to be packed gently into bony voids or gaps of the skeletal system (extremities and pelvis), and may be used without hydration or hydrated with bone marrow aspirate or blood. The device provides a bone void filler that is resorbed and replaced with host bone during the healing process.

Device Description

REBOSSIS is a synthetic, resorbable bone void filler. It is composite material consisting of (by weight) 40% beta-tricalcium phosphate (B-TCP), 30% siloxane-containing vaterite (a form of calcium carbonate, CaCO3), and 30% poly(L-lactide). The electrospinning process used in manufacturing REBOSSIS results in a glass wool-like physical form. Due to its physical form, REBOSSIS is flexible and can easily fill defects in appropriate amounts.

AI/ML Overview

The provided text is a 510(k) summary for the medical device REBOSSIS, a resorbable calcium salt bone void filler. It details the device's characteristics, intended use, and substantial equivalence to a predicate device. However, it does not include specific acceptance criteria or a study with performance data in the format of acceptance criteria and reported device performance. The document focuses on pre-clinical testing for material characterization and animal studies to demonstrate substantial equivalence, rather than human clinical trials with defined performance endpoints.

Therefore, many of the requested details cannot be extracted directly from the provided text.

Here's a breakdown of what can and cannot be answered based on the provided text:

1. A table of acceptance criteria and the reported device performance

Cannot be provided. The document does not define explicit acceptance criteria or report device performance against specific targets in a table format. It describes the scope of testing performed (material characterization, biocompatibility, and animal studies) to demonstrate substantial equivalence, not to meet pre-defined performance thresholds for clinical efficacy in humans.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Sample size for animal testing: The document mentions "Animal testing performed to demonstrate substantial equivalence included determination of radiographic, histologic and histomorphometric characteristics of the subject device and the predicate device in a rabbit distal femoral condyle critical-sized defect model." It further states, "The baseline (time 0) animals included REBOSSIS (dry) and Actifuse Shape (dry) to provide information on the initial amount of material implanted to fill the defects. Autograft bone filled defects (positive control) and empty unfilled defects (negative control) also were evaluated at 6 weeks and 12 weeks."
- Interpretation: While it specifies using a rabbit model and control groups, the exact number of animals per group or the total sample size is not explicitly stated.
Data provenance: Not explicitly stated but the manufacturer is ORTHOREBIRTH Co., Ltd. from Japan, suggesting the studies could have been conducted there or through contract research organizations globally. The document does not specify whether the data is retrospective or prospective. Given it's a pre-clinical animal study, it would inherently be prospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable/Not provided. This question pertains to clinical studies often involving human image interpretation or diagnostic outcomes. The provided document describes pre-clinical animal studies involving radiographic, histologic, and histomorphometric evaluations. While expert interpretation would have been involved in these analyses, the document does not specify the number or qualifications of experts for "ground truth" establishment in a clinical context.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable/Not provided. Adjudication methods are typically used in clinical trials involving multiple human readers for diagnostic tasks. This document describes pre-clinical animal studies; therefore, an adjudication method in this context is not relevant and not mentioned.

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 study is a clinical study involving human readers and typically an AI component. The provided document explicitly states: "No clinical data were included in this submission." Therefore, no MRMC study or evaluation of human reader improvement with AI assistance was performed or reported.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

No. This question is relevant for AI/algorithm-based devices. REBOSSIS is a physical medical device (bone void filler), not an AI algorithm. Therefore, "standalone algorithm performance" is not applicable.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

For animal studies: The "ground truth" was established through standard scientific methods for pre-clinical animal models:
- Radiographic evaluation: Interpreting X-rays or micro-CT images.
- Histologic evaluation: Microscopic examination of tissue samples.
- Histomorphometric analysis: Quantitative analysis of microscopic tissue structures.
- In these types of studies, experienced veterinary pathologists and radiologists would typically establish findings, which serve as the "ground truth" for the animal model's response to the implant.

8. The sample size for the training set

Not applicable/Not provided. This question pertains to machine learning algorithms. REBOSSIS is a physical device, not an AI algorithm, so there is no "training set."

9. How the ground truth for the training set was established

Not applicable/Not provided. As there is no training set for an AI algorithm, this question is not applicable.

Summary

{0}------------------------------------------------

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

October 29, 2014

ORTHOREBIRTH Co., Ltd. % Kevin A. Thomas, Ph.D. PaxMed International, LLC 12264 El Camino Real, Suite 400 San Diego, California 92130

Re: K142090

Trade/Device Name: REBOSSIS Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MQV Dated: July 31, 2014 Received: August 1, 2014

Dear Dr. Thomas:

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. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

{1}------------------------------------------------

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Lori A. Wiggins -S

for Mark N. Melkerson Director Division of Orthopedic Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number: K142090

Device Name: REBOSSIS

Prescription Use X (Part 21 CFR 801 Subpart D)

Over-The-Counter Use AND/OR (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Page 1 of 1

{3}------------------------------------------------

510(k) Summary

ORTHOREBIRTH Co., Ltd.

REBOSSIS

October 28, 2014

ADMINISTRATIVE INFORMATION

Manufacturer Name	ORTHOREBIRTH Co., Ltd.3-17-43 Chigasaki HigashiTsuzuki-ku Yokohama, Kanagawa, 224-0033, JapanTelephone: +81-45532-3650Fax: +81-45532-3691
Official Contact	Yasutoshi NishikawaCEO
Representative/Consultant	Kevin A. Thomas, PhDFloyd G. LarsonPaxMed International, LLC12264 El Camino Real, Suite 400San Diego, CA 92130Telephone: +1 (858) 792-1235Fax: +1 (858) 792-1236Email: kthomas@paxmed.com flarson@paxmed.com

DEVICE NAME AND CLASSIFICATION

Trade/Proprietary NameCommon Name	REBOSSISFiller, bone void, calcium compoundResorbable calcium salt bone void filler device21 CFR 888.3045, Class IIMOV
Classification NameClassification RegulationsProduct Code
Classification PanelReviewing Branch	Orthopaedic and Rehabilitation Devices PanelRestorative and Repair Devices Branch (RRDB)

{4}------------------------------------------------

INTENDED USE

DEVICE DESCRIPTION

PERFORMANCE DATA

Pre-clinical testing data submitted, referenced, or relied upon to demonstrate substantial equivalence included chemical composition, physical properties, biocompatibility, and performance characteristics. Biocompatibility testing was performed using methods described in ISO 10993-1, ISO 10993-3, ISO 10993-5, ISO 10993-6, ISO 10993-10, ISO 10993-11, USP 36 <85> and USP 36 <151>.

Material characterization performed included: true density by pycnometry, chemical composition by energy dispersive x-ray spectrometry (EDX), trace elemental analysis by inductively coupled plasma/mass spectroscopy (ICP/MS), residual solvents by the methods described in USP <467>, surface microstructure by scanning electron microscopy (SEM), and polymer properties by gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). The in vitro release kinetics of Si, Ca and P ions were measured using inductively coupled plasma spectroscopy (ICP) at multiple time points after up to 14 days in simulated body fluid. SEM, EDX, and Fourier transform infrared spectroscopy (FTIR) also were performed at time 0 and after 14 days in simulated body fluid.

Animal testing performed to demonstrate substantial equivalence included determination of radiographic, histologic and histomorphometric characteristics of the subject device and the predicate device in a rabbit distal femoral condyle critical-sized defect model. Each material was evaluated with three (3) hydration conditions: no hydration (dry, material alone), hydrated with autologous blood, and hydrated with autologous bone marrow aspirate. Hydration with blood or bone marrow aspirate was 1:1 by volume.

{5}------------------------------------------------

The study time points included baseline (time 0), 6 weeks, and 12 weeks. The baseline (time 0) animals included REBOSSIS (dry) and Actifuse Shape (dry) to provide information on the initial amount of material implanted to fill the defects. Autograft bone filled defects (positive control) and empty unfilled defects (negative control) also were evaluated at 6 weeks and 12 weeks. Evaluation endpoints included high-resolution radiography, micro-computed tomography (micro-CT) imaging, undecalcified histologic evaluation, and histomorphometric analysis.

No clinical data were included in this submission.

EQUIVALENCE TO MARKETED DEVICE

The subject device is substantially equivalent in indications and design principles to the following predicate device:

K080736. Actifuse™ Shape. ApaTech Limited

The subject device and the predicate device are bone void fillers that are intended for bony voids or gaps that are not intrinsic to the stability of the bony structure (extremity and pelvis) and both are indicated for use without hydration or hydrated with bone marrow aspirate or blood. Any differences in the technological characteristics between the subject and predicate devices do not raise different questions of safety or effectiveness.

The data included in this submission demonstrate substantial equivalence to the predicate device listed above.

Overall, the subject device has the following similarities to the predicate devices:

has the same intended use, ●
. uses the same operating principle.
incorporates the same basic design,
incorporates the same or very similar materials, and ●
has similar packaging and is sterilized using the same materials and processes. .

Regulation Number and Section

§ 888.3045 Resorbable calcium salt bone void filler device.

(a)
Identification. A resorbable calcium salt bone void filler device is a resorbable implant intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure.(b)
Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA.” See § 888.1(e) of this chapter for the availability of this guidance.