NanoFUSE® DBM is indicated to be gently placed into bony voids or gaps of the skeletal system that are not intrinsic to the stability of the bony structure. It is indicated to be placed into bony voids or gaps of the skeletal structure (e.g., the extremities and pelvis). These defects may be surgically created osseous defects or osseous defects created by traumatic injury to the bone. The product provides a bone graft substitute that remodels into the recipient's skeletal system.

Device Description

NanoFUSE® DBM is a malleable, putty-like, bone-void filler. The product is comprised of human demineralized bone matrix (DBM) and synthetic calcium phosphor-silicate particulate material particles (45s5 bioactive glass), both coated with gelatin derived from porcine skin. These coated particles are packaged dry in a single use, polypropylene syringe (20 cc or 3 cc), double-wrapped in peel-back pouches, and final packaged in a dust cover paperboard carton. The 20 cc syringe will be filled with either of two different fill quantities of dry powder, identified as 10 cc or 5 cc final product volume. The 3 cc syringe will be filled with dry powder, identified as 2 cc final product volume. NanoFUSE® DBM is intended for single patient use only. At point of use, the surgeon will reconstitute the product with an appropriate sterile solution of his/her choice (sterile saline, water for injection). The coated particles rehydrate in less than 30 seconds and do not require mixing to form a uniform paste or putty. The material is then gently extruded by the surgeon into the appropriate bone voids. NanoFUSE® DBM is progressively resorbed and replaced by host bone during the osteo-remodeling process.

AI/ML Overview

Note that the provided text is a 510(k) summary for a medical device (NanoFUSE® DBM) seeking substantial equivalence to predicate devices, not a clinical study report. Therefore, it does not contain the detailed information about acceptance criteria, specific performance metrics, sample sizes for test sets, expert qualifications, adjudication methods, or direct comparative effectiveness studies with human readers that are typically found in a clinical study demonstrating performance against predefined acceptance criteria.

The submission focuses on demonstrating substantial equivalence based on similar materials, design, intended use, and technological characteristics, not on proving specific performance metrics against a predetermined acceptance criterion through a clinical trial or a standalone performance study as described in your request.

However, I can extract the relevant information that is present regarding the device's characteristics and the changes discussed in the 510(k).

Here's an attempt to answer your questions based only on the provided document, highlighting where information is not present or not directly applicable to your request format:

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

This document does not present quantitative acceptance criteria or corresponding reported device performance metrics in the way a clinical study would. The summary focuses on substantial equivalence to a predicate device by comparing technological characteristics. The primary "performance" discussed is related to osteoinductivity testing, which is a screening method for the DBM component, not a final device performance metric with acceptance criteria.

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

Test Set Sample Size: Not specified in terms of a clinical test set. The document mentions testing "each lot of DBM" for osteoinductivity, using either an in vitro bioassay or an in vivo athymic rat model. There's no sample size given for these tests in the context of device performance.
Data Provenance: The DBM is human-derived, but the country of origin for the data (if it were a clinical study) is not mentioned. The athymic rat model suggests animal testing, not human clinical data directly. This is a regulatory submission from a US-based company (Alachua, FL).
Retrospective/Prospective: Not applicable to this type of regulatory submission. The osteoinductivity testing described is part of quality control for the raw material (DBM).

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. The document discusses in vitro bioassays and in vivo athymic rat models for osteoinductivity, not human expert assessment of a test set. There's no "ground truth" established by human experts in the context of device performance as you describe.

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

Not applicable. There is no human expert assessment or adjudication described in this document for a test set.

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

Not applicable. This device is a bone void filler, not an AI-assisted diagnostic tool.

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

Not applicable. This is not an algorithmic device.

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

The closest to "ground truth" mentioned pertains to the osteoinductivity of the DBM component:

Osteoinductivity: Assessed through in vitro bioassays or an in vivo athymic rat model. The document states, "Results from this bioassay were correlated to the athymic rat model." This suggests these animal/lab models serve as the "truth" for osteoinductive potential.

8. The sample size for the training set

Not applicable. This is not an AI/machine learning device that uses a training set.

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

Not applicable.

Summary of Device and Regulatory Context:

The NanoFUSE® DBM is a bone void filler indicated for use in bony voids or gaps of the skeletal system. The 510(k) submission (K120279) primarily addresses a change in the osteoinductivity testing method for the DBM component used in the device. The applicant seeks to use either the original in vitro bioassay or an in vivo athymic rat model. The FDA's determination is that this change does not alter the fundamental scientific technology and thus the device remains substantially equivalent to its predicate. The document focuses on material composition, intended use, and manufacturing processes rather than performance metrics from a comparative clinical trial.

Summary

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(120279 SE 1 OF 3

anotherapeutics

6 2019

510(k) SUMMARY OF SAFETY & EFFECTIVENESS

NanoFUSE® DBM

Date:

January 27, 2012

Submitted by:

Nanotherapeutics, Inc. 13859 Progress Blvd., Suite 300 Alachua, FL 32615

Representative:

Gregg Ritter, MS, RAC, CTBS Regulatory Affairs Manager Phone: (386) 462-9663 FAX: (386) 462-2087

NanoFUSE® DBM Proprietary Name: Common Name: Bone Void Filler, Bone Graft Substitute Classification Name: Filler, Calcium Sulfate Preformed Pellets, 21 CFR § 888.3045 Classification Codes: MQV, MBP - Class II

Predicate Devices:

Trade/Proprietary Name	Manufacturer	510(k) Number
Origen™ DBM with Bioactive Glass	Nanotherapeutics	K062459, K110976
(NanoFUSE® DBM)

Description:

At point of use, the surgeon will reconstitute the product with an appropriate sterile solution of his/her choice (sterile saline, water for injection). The coated particles rehydrate in less than 30 seconds and do not require mixing to form a uniform paste or putty. The material is then gently extruded by the surgeon into the appropriate bone voids. NanoFUSE® DBM is progressively resorbed and replaced by host bone during the osteo-remodeling process.

Indications for Use:

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K120279
PAGE 2 OF 3

the skeletal structure (e.g., the extremities and pelvis). These defects may be surgically created osseous defects or osseous defects created by traumatic injury to the bone. The product provides a bone graft substitute that remodels into the recipient's skeletal svstem.

Technological Characteristics:

The applicant version of NanoFUSE® DBM is identical to the currently legally marketed medical device NanoFUSE® DBM, also manufactured by Nanotherapeutics, Inc. with respect to materials. design, and intended use. The applicant version is comprised of human demineralized bone matrix (DBM) and synthetic calcium phosphor-silicate particulate material particles (45s5 bioactive glass), both coated with gelatin derived from porcine skin. It is provided dry and is reconstituted at the point of use into a paste-like, malleable form that can be molded or manipulated into bony defects.

NanoFUSE® DBM is reconstituted by the addition of fluid and waiting 30 seconds before expelling the contents from the syringe. At 30 seconds, the product extrudes as a very fluid paste and, with time, the gelatin carrier absorbs the fluid, becomes progressively thicker, and eventually sets in a rubbery mass.

Currently, each lot of DBM used in manufacturing the predicate Origen DBM® with Bioactive Glass (NanoFUSE® DBM) is screened for osteoinductivity in an in vitro bioassay. Each lot of DBM used in manufacturing the applicant version of NanoFUSE® DBM will be screened for osteoinductivity with either the in vitro bioassay originally submitted or the in vivo athymic rat model herein submitted.

The scientific technology of NanoFUSE® DBM applicant product. using in vivo testing for osteoinductivity, is identical to the technology used in the FDA cleared predicates. (K062459, K110976)

ComparisonFeature	NanoFUSE® DBM -Predicate	NanoFUSE® DBM- Applicant
Form	Syringe	Same
Materials ofConstruction	DBM, bioactive glass,gelatin	Same
ComparableSizes	Yes	Yes
OsteoinductivityAssay	Cell bioassay	in vivo athymic ratimplant or cellbioassay
Sterility	Yes - Radiation	Same

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K120279 PAGE 3 OF 3

Osteoinductivity Potential:

athymic rat model. Results from this bioassay were correlated to the athymic rat model. Testing each lot of DBM with this cell bioassay or athymic rat model assures that only DBM with osteoinductive potential is used in NanoFUSE® DBM. The combination of DBM. bioactive glass, and porcine gelatin has not been evaluated for osteoinductivity; therefore, it is unknown to what extent the formulation components may alter the osteoinductive character of the DBM. It is unknown how the OI of the DBM component, measured via the in vitro bioassay or athymic rat model, will correlate with human clinical performance of NanoFUSE® DBM.

The change in osteoinductivity potential testing for the DBM does not

alter the fundamental scientific technology of the device and it does not have an effect on the viral clearance and inactivation of the device. A panel of model potential human viruses representing various virus types, sizes, shapes and genomes has previously been evaluated. The viral inactivation testing demonstrated that suitable viral inactivation potential was obtained by the processing method for

a wide spectrum of potential human viruses.

according to ISO 10993.

(NanoFUSE® DBM).

Each lot of DBM incorporated into NanoFUSE® DBM is evaluated for osteoinductive (OI) potential using an in vitro bioassay or in vivo

Viral Clearance and Inactivation:

Safety and Effectiveness:

The change in osteoinductivity potential testing for the DBM does not alter the fundamental scientific technology of the device and it does not have an effect on the biocompatibility of the device. Biocompatibility testing, pre-clinical animal testing and in vitro bench testing has previously been conducted to evaluate the biological safety and performance characteristics of NanoFUSE® DBM

The change in osteoinductivity potential testing for the DBM does not alter the fundamental scientific technology of the device. Based on the testing provided, the submitted change does not have an effect on the safety or effectiveness of the device. Therefore, the applicant version of NanoFUSE® DBM is substantially equivalent to the currently cleared version of Origen DBM® with Bioactive Glass

Substantial Equivalence:

ર-3

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an emblem featuring a stylized depiction of an eagle or bird-like figure.

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

Nanotherapeutics, Incorporated % Mr. Gregg Ritter, MS, RAC, CTBS Regulatory Affairs Manager 13859 Progress Boulevard, Suite 300 Alachua, Florida 32615

APR - 6 2012

Re: K120279

Trade/Device Name: NanoFUSE® DBM Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MQV, MBP Dated: January 27, 2012 Received: January 30, 2012

Dear Mr. Ritter:

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 of any I cated butter and registements, 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 803); good manufacturing practice requirements as set 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.

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Page 2 - Mr. Gregg Ritter, MS, RAC, CTBS

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours,

Mark N. Melkerso Director Division of Surgical, Orthopedic and Restorative Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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nanotherapeutics

INDICATIONS FOR USE

510(k) Number (if known): K120279

Device Name: NanoFUSE® DBM

Indications for Use:

× Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

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

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Signature

(Division Sign-Off) Division of Surgical, Orthopedic, and Restorative Devices

510(k) Number K120279

4-1

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.