K Number
K172573
Device Name
ReBOSSIS85
Date Cleared
2017-12-15

(109 days)

Product Code
Regulation Number
888.3045
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

ReBOSSIS85 is 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 created from traumatic injury to the bone. ReBOSSIS85 is indicated to be packed gently into bony voids or gaps of the skeletal system (extremities, pelvis, and posterolateral spine). In the extremities and pelvis ReBOSSIS85 may be used without hydrated with blood. In the posterolateral spine ReBOSSIS85 is to be used hydrated with bone marrow aspirate and mixed with autograft bone. The device provides a bone void filler that is resorbed with host bone during the healing process.

Device Description

ReBOSSIS85 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-co-glycolide). The electrospinning process used in manufacturing ReBOSSIS85 results in a glass wool-like physical form. Due to its physical form, ReBOSSIS85 is flexible and can easily fill defects in appropriate amounts. ReBOSSIS85 is provided sterile for single-patient, single-use.

AI/ML Overview

This document describes a 510(k) premarket notification for ReBOSSIS85, a resorbable calcium salt bone void filler device. The submission aims to demonstrate substantial equivalence to legally marketed predicate devices.

Here's an analysis of the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly list acceptance criteria in the form of specific performance thresholds for ReBOSSIS85. Instead, the "Performance Data" section details the types of non-clinical tests performed to demonstrate substantial equivalence, and the "Equivalence to Marketed Device" section presents a comparative table between the subject device and predicate devices. The ultimate "acceptance criterion" in a 510(k) context is demonstrating substantial equivalence to a predicate device, meaning it is as safe and effective.

However, we can infer performance areas assessed based on the tests conducted. The key performance comparison is drawn from the in vivo animal study.

Acceptance Criteria (Inferred from study type)Reported Device Performance (ReBOSSIS85 vs. Predicate K140375)
Radiographic characteristics (bone formation, defect filling etc.)"performance of the subject ReBOSSIS85 device was equivalent to that of the predicate device K140375"
Histologic characteristics (tissue reaction, new bone formation, material resorption)"performance of the subject ReBOSSIS85 device was equivalent to that of the predicate device K140375"
Histomorphometric characteristics (quantitative analysis of bone formation, material volume)"performance of the subject ReBOSSIS85 device was equivalent to that of the predicate device K140375"
Chemical characterizationDetailed analysis of composition (B-TCP, siloxane-containing vaterite, poly(L-lactide-co-glycolide)), Si content, material properties (density, trace elements, residual solvents, surface microstructure, polymer properties).
Physical characterizationGlass wool-like form, nominal fiber diameter range (3 μm to 150 μm), max diameter (250 μm), approximately 98% porosity (dry).
Sterilization validationMethods described in AAMI/ANSI/ISO 11137-1, AAMI/ANSI/ISO 11137-2.
Shelf life validation (sterile barrier and product)Methods described in ASTM F1140/F1140M, and ASTM F2096.
BiocompatibilityMethods described in AAMI/ANSI/ISO 10993-1, -5, -10, -11, -12; Pyrogenicity and bacterial endotoxin (USP 39-NF 34 <151> and <85>).
In vitro release kineticsRelease of Si, Ca, and P ions, pH of the solution, material imaging by SEM, polymer weight-average molecular weight by GPC.

2. Sample size used for the test set and the data provenance

  • Test Set Description: The primary test set mentioned for performance evaluation is an in vivo animal study in a rabbit posterolateral fusion model.
  • Sample Size: The document does not specify the exact number of animals (sample size) used in this rabbit study.
  • Data Provenance: The study was "Animal testing performed to demonstrate substantial equivalence." The document does not specify the country of origin but implies it was conducted by the manufacturer or a contracted lab for regulatory submission. It is by nature prospective observational for the purpose of evaluating the device's performance over time in a biological system.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document mentions histological analysis and grading according to AAMI/ANSI/ISO 10993-6 (Annex E). This implies expert evaluation of tissue samples. However, the document does not specify the number of experts or their specific qualifications (e.g., "pathologist with X years of experience") used to establish the ground truth (histologic grades, interpretations of radiographs/micro-CT) for the animal study.

4. Adjudication method for the test set

The document does not specify an adjudication method for the evaluation of the animal study results (radiography, manual palpation, biomechanical testing, micro-CT, histologic analysis, histomorphometric analysis). It only states that "Evaluation endpoints included radiography, manual palpation, non-destructive biomechanical testing, micro-computed tomography (micro-CT) imaging, non-decalcified histologic analysis, and non-decalcified histomorphometric analysis."

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a bone void filler (a physical medical device), not an AI-powered diagnostic or assistive tool for human readers. Therefore, the question about human reader improvement with 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. As mentioned, this is a physical medical device, not an algorithm or software.

7. The type of ground truth used

For the animal study:

  • Radiographic characteristics: Likely based on expert review of X-ray images.
  • Histologic characteristics: Expert interpretation of stained tissue sections by trained histologists/pathologists. Graded according to AAMI/ANSI/ISO 10993-6 (Annex E).
  • Histomorphometric analysis: Quantitative measurements derived from histological sections, providing objective metrics about bone formation, material degradation, etc. This is based on direct measurement, not expert consensus in the same way as qualitative grading.
  • Micro-computed tomography (micro-CT) imaging: Provides detailed 3D structural information that can be quantitatively analyzed.
  • Manual palpation: A subjective assessment.
  • Non-destructive biomechanical testing: Objective quantitative measurements of mechanical properties.

Overall, the ground truth for the in-vivo study appears to be a combination of expert interpretation (histology, radiography) and objective measurements (histomorphometry, biomechanics, micro-CT).

8. The sample size for the training set

Not applicable. This document is for a physical medical device (bone void filler), not a machine learning or AI model. Therefore, there is no "training set" in the context of AI.

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

Not applicable. As this is not an AI/ML device, there is no training set or ground truth in that context. The "ground truth" discussed in point 7 relates to the evaluation of the device's biological performance.

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December 15, 2017 ORTHOREBIRTH Co., Ltd. % Kevin Thomas, Ph.D. Vice President and Director of Regulatory Affairs PaxMed International, LLC 12264 El Camino Real, Suite 400 San Diego, California 92130

Re: K172573

Trade/Device Name: ReBOSSIS85 Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MOV Dated: November 15, 2017 Received: November 16, 2017

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

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manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Vincent J. Devlin -S

for

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

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known)

K172573

Device Name

ReBOSSIS85

Indications for Use (Describe)

ReBOSSIS85 is 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 created from traumatic injury to the bone. ReBOSSIS85 is indicated to be packed gently into bony voids or gaps of the skeletal system (extremities, pelvis, and posterolateral spine). In the extremities and pelvis ReBOSSIS85 may be used without hydrated with blood. In the posterolateral spine ReBOSSIS85 is to be used hydrated with bone marrow aspirate and mixed with autograft bone. The device provides a bone void filler that is resorbed with host bone during the healing process.

Type of Use (Select one or both, as applicable)
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X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary ReBOSSIS85 ORTHOREBIRTH Co., Ltd.

August 25, 2017

ADMINISTRATIVE INFORMATION

Manufacturer NameORTHOREBIRTH Co., Ltd.
3-17-43 Chigasaki Higashi
Tsuzuki-ku Yokohama, Kanagawa, 224-0033, Japan
Telephone:+81-45532-3650
Fax:+81-45532-3691
Official ContactYasutoshi Nishikawa, CEO
Representative/ConsultantKevin A. Thomas, PhD
Floyd G. Larson, MS, MBA
PaxMed International, LLC
12264 El Camino Real, Suite 400
San Diego, CA 92130
Telephone:+1-858-792-1235
Fax:+1-858-792-1236
Email:kthomas@paxmed.com
flarson@paxmed.com

DEVICE NAME AND CLASSIFICATION

Trade/Proprietary NameReBOSSIS85
Common NameFiller, bone void, calcium compound
Classification NameResorbable calcium salt bone void filler device
Classification Regulations21 CFR 888.3045, Class II
Product CodeMQV
Classification PanelOrthopaedic and Rehabilitation Devices Panel
Reviewing BranchRestorative and Repair Devices Branch (RRDB)

PREDICATE DEVICE INFORMATION

Primary Predicate K140375, MASTERGRAFT® Strip; MASTERGRAFT® Putty, Medtronic Sofamor Danek USA, Inc.

Reference Predicate K170620, ReBOSSIS85, ORTHOREBIRTH Co., Ltd.

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INDICATIONS FOR USE

ReBOSSIS85 is 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 created from traumatic injury to the bone. ReBOSSIS85 is indicated to be packed gently into bony voids or gaps of the skeletal system (extremities, pelvis, and posterolateral spine). In the extremities and pelvis ReBOSSIS85 may be used without hydration or hydrated with blood. In the posterolateral spine ReBOSSIS85 is to be used hydrated with bone marrow aspirate and mixed with autograft bone. The device provides a bone void filler that is resorbed and replaced with host bone during the healing process.

DEVICE DESCRIPTION

ReBOSSIS85 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-co-glycolide). The electrospinning process used in manufacturing ReBOSSIS85 results in a glass wool-like physical form. Due to its physical form, ReBOSSIS85 is flexible and can easily fill defects in appropriate amounts. ReBOSSIS85 is provided sterile for single-patient, single-use.

PERFORMANCE DATA

Non-clinical testing data submitted to demonstrate substantial equivalence included chemical characterization, physical characterization, sterilization, shelf life validation, biocompatibility, and in vivo (animal) performance.

Characterization of the ReBOSSIS85 material included: true density by pycnometry, chemical composition by energy dispersive x-ray spectrometry (EDX), trace elemental analysis by inductively coupled plasmalmass spectroscopy (ICP-MS) and inductively coupled plasma/atomic emission spectroscopy (ICP-AES), 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). ReBOSSIS85 also was characterized by a variety of techniques at baseline (time zero) and after immersion in TRIS-HCl buffer media at 37 °C. The evaluations performed included: in vitro release kinetics of Si, Ca, and P ions using inductively coupled plasma spectroscopy (ICP); the pH of the solution; imaging of the material (after drying) by scanning electron microscopy (SEM); and polymer weight-average molecular weight by gel permeation chromatography (GPC).

Sterilization validation, sterile barrier shelf life, and product shelf life testing were performed using methods described in AAMI/ANSI/ISO 11137-1, AAMI/ANSI/ISO 11137-2, ASTM F1140/F1140M, and ASTM F2096.

Biocompatibility testing was performed using methods described in AAMI/ANSI/ISO 10993-1. AAMI/ANSI/ISO 10993-5, ISO 10993-10, ISO 10993-11, and ISO 10993-12. Pyrogenicity and bacterial endotoxin testing were performed using methods described in USP 39-NF 34 <151> and USP 39-NF 34 <85>.

Animal testing performed to demonstrate substantial equivalence included determination of the radiographic, histologic, and histomorphometric characteristics of the subject device and the predicate device in a rabbit posterolateral fusion model. The study time points included 4 weeks, and 12 weeks. Evaluation endpoints included radiography, manual palpation, non-destructive biomechanical testing, micro-computed tomography (micro-CT) imaging, non-decalcified histologic analysis, and non-decalcified histomorphometric analysis. Histology sections also were graded according to AAMI/ANSVISO 10993-6 (Annex E).

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EQUIVALENCE TO MARKETED DEVICE

The subject device is substantially equivalent in indications and design principles to the predicate devices listed above. A summary table comparing the Indications for Use statement and the technological characteristics of the subject device and the predicate devices is provided in the following table.

Subject DevicePrimary Predicate DeviceReference Predicate Device
ComparisonReBOSSIS85ORTHOREBIRTH Co., Ltd.K140375MASTERGRAFT® Strip; MASTERGRAFT®PuttyMedtronic Sofamor Danek USA, Inc.K170620ReBOSSIS85ORTHOREBIRTH Co., Ltd.
Indications for UseStatementReBOSSIS85 is intended for use in bony voids orgaps that are not intrinsic to the stability of thebony structure. These defects may be surgicallycreated osseous defects or osseous defects createdfrom traumatic injury to the bone. ReBOSSIS85is indicated to be packed gently into bony voidsor gaps of the skeletal system (extremities, pelvis,and posterolateral spine). In the extremities andpelvis ReBOSSIS85 may be used withouthydration or hydrated with blood. In theposterolateral spine ReBOSSIS85 is to be usedhydrated with bone marrow aspirate and mixedwith autograft bone. The device provides a bonevoid filler that is resorbed and replaced with hostbone during the healing process.MASTERGRAFT® Putty combined with eitherautogenous bone marrow, and/or sterile water,and/or autograft is indicated as a bone void fillerfor bony voids or gaps that are not intrinsic to thestability of the bony structure: Additionally.MASTERGRAFT® Putty can be used withautograft as a bone graft extender.MASTERGRAFT® Putty is to be gently packedinto bony voids or gaps of the skeletal system(e.g., the posterolateral spine, pelvis. ilium.and/or extremities). These defects may besurgically created osseous defects or osseousdefects created from traumatic injury to the bone.MASTERGRAFT® Putty resorbs and is replacedwith bone during the healing process.ReBOSSIS85 is intended for use in bony voids orgaps that are not intrinsic to the stability of thebony structure. These defects may be surgicallycreated osseous defects or osseous defectscreated from traumatic injury to the bone.ReBOSSIS85 is indicated to be packed gentlyinto bony voids or gaps of the skeletal system(extremities and pelvis), and may be usedwithout hydration or hydrated with blood. Thedevice provides a bone void filler that is resorbedand replaced with host bone during the healingprocess.
Product CodeMQVMQVMQV
Intended UseBone void filler for skeletal system(extremities, pelvis, and posterolateral spine)Bone void filler for skeletal system(extremities, pelvis, and posterolateral spine)Bone void filler for skeletal system(extremities, pelvis)
Design
FormGlass wool-like, produced by electrospinningGranules uniformly dispersed in collagenscaffoldGlass wool-like, produced by electrospinning
Granule SizeNot applicable0.5 mm - 1.6 mm in diameterNot applicable
Fiber Sizenominal diameter range: 3 μm to 150 μmspecification of maximum diameter: 250 μmNot applicablenominal diameter range: 3 μm to 150 μmspecification of maximum diameter: 250 μm
PorosityApproximately 98 % (dry, no hydration)Granules 80%Approximately 98 % (dry, no hydration)
Materials
Calcium saltsβ-tricalcium phosphate, 40 % by weightSiloxane-containing vaterite (SiV), 30 % byweightβ-tricalcium phosphate (85%) andHydroxyapatite (15%)β-tricalcium phosphate, 40 % by weightSiloxane-containing vaterite (SiV), 30 % byweight
SiliconApproximately 0.7 % by weightRange, 0.5 % - 1 % by weightNot applicableApproximately 0.7 % by weightRange, 0.5 % - 1 % by weight
Scaffold/BinderPoly(L-lactide-co-glycolide), 30% by weightType I bovine collagenPoly(L-lactide-co-glycolide), 30% by weight
How Provided
SizesProvided in 0.4, 0.7, 1, and 2 gram packagesApproximate volume:10-50 cc (dry, no hydration)4-20 cc (after hydration)Provided in 0.75 cc, 1.5 cc, 3.0 cc, 6.0 cc,and 9.0 cc packagesProvided in 0.5, 1, and 2 gram packagesApproximate volume:13-50 cc (dry, no hydration)5-20 cc (after hydration)
Hydration prior touseBone marrow aspirate (required)Bone marrow aspirate and/or sterile water(required)Blood (optional)
SterilityProvided sterile to end-userProvided sterile to end-userProvided sterile to end-user
SterilizationGamma irradiationNot statedGamma irradiation
UsageSingle-patient, single-useSingle-patient, single-useSingle-patient, single-use
Table of Substantial Equivalence
----------------------------------

The primary predicate device is K140375 for substantial equivalence in the animal model performance testing. The reference predicate device is K170620 in support of substantial equivalence in the physical form and the material composition.

The subject device and the primary predicate device have intended uses, the same product classification and product code (MQV), and have similar Indications for Use statements. The subject device and the primary predicate devices are bone void fillers that are intended for bony voids or gaps that are not intrinsic to the stability

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of the bony structure. The subject device and primary predicate device are indicated for use as in the posterolateral spine with autograft bone (extender), and the subject device and primary predicate device are to be hydrated with bone marrow aspirate (primary predicate device with sterile water). Although the subject device and the primary predicate device have slightly different Indications for Use language, these differences do not change the intended use as a bone void filler in the posterolateral spine.

The subject device and the predicate devices all incorporate materials within a polymer scaffold or binder. The subject device polymer scaffold is poly(L-lactide-co-glycolide), the predicate K140375 scaffold is type I bovine collagen. The subject device is identical to the reference predicate device K170620. The subject device and the predicate devices are provided sterile for single-use in similar ranges of graft volumes.

The radiographic, histologic, and histomorphometric performance of the subject device were compared to that of the primary predicate device K140375 in a rabbit posterolateral fusion model. The results of the study demonstrated that the performance of the subject ReBOSSIS85 device was equivalent to that of the predicate device K140375.

No clinical data were included in this submission.

CONCLUSION

The subject device and the predicate devices have the same intended use, have similar technological characteristics, and are made of similar materials. The subject and predicate devices are packaged in similar materials and are sterilized using similar methods. The data included in this submission demonstrate substantial equivalence to the predicate device listed above.

§ 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.