Rafugen™ DBM is intended for use as a bone void filler in bony voids or gaps of the skeletal system (i.e., pelvis and extremities) not intrinsic to the stability of the bony structure. The voids or gaps may be surgically created defects or defects created by traumatic injury to the bone. Rafugen™ DBM is resorbed/remodeled and is replaced by host bone during the healing process.

Device Description

Rafugen™ DBM is a human bone allograft product containing human DBM (demineralized bone matrix), CMC (carboxymethyl cellulose), Starch and Glycerol. It is intended for use in filling bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure. Rafugen™ DBM is a ready-to use moldable gel formulation provided pre-filled in syringes of various volumes and is intended for single patient use. It is offered in six volumes: 0.25, 0.5, 1.0, 3.0, 5.0, and 10.0 cc. The Rafugen™ DBM can be either directly applied into the defect from the syringe, using the cap tip, or extruded for molding and insertion into the defect by hand.

AI/ML Overview

The provided text is a 510(k) summary for the device Rafugen™ DBM, which is a resorbable calcium salt bone void filler. This document is a regulatory submission for market clearance and not a detailed clinical study report. Therefore, it does not contain the typical information one would find in a clinical trial publication regarding acceptance criteria and performance of a device based on clinical endpoints or reader studies for AI.

However, based on the non-clinical performance data section, I can extract information related to the device's technical acceptance criteria and the studies performed to meet them.

Here's a breakdown of the requested information based on the provided text, recognizing the limitations of the document type for certain aspects:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria/Test	Reported Device Performance
Biocompatibility	Biocompatibility testing	"The final composition of Rafugen™ DBM was found to be biocompatible and to meet its design specifications."
Sterility	Sterility testing	Performed (mentioned as a conducted test, but specific results or acceptance criteria are not detailed beyond the implication that it passed).
Chemical/Physical Properties	Chemical and physical properties testing	Performed (mentioned as a conducted test, but specific results or acceptance criteria are not detailed beyond the implication that it passed and the product being "substantially equivalent to the predicate device with respect to materials... and an inert resorbable nontissue additive or carrier").
Material Mediated Pyrogenicity	Endotoxin level below 0.5 EU/mL	"Under the conditions of this study, no endotoxin level showed above 0.5 EU/mL in all five batches. The test extract was judged as non-pyrogenic, and the test sample satisfied the requirements for the absence of pyrogens."
Osteoinductive Potential	Positive result in athymic rat assay (ectopic pouch model)	"Yes, per athymic rat assay." "The testing for osteoinductive potential of both devices was demonstrated using a validated athymic rat assay."
Inactivation of Model Viruses	Validation of processing to demonstrate inactivation of a panel of model viruses	"Validation was performed for the Rafugen™ DBM processing to demonstrate inactivation of a panel of model viruses." (Implied successful validation, but specific inactivation levels or acceptance criteria are not provided).
Performance (Bone Growth/Remodeling)	Equivalent bone growth and remodeling to predicate in a rabbit femoral defect model	"Bone growth and remodeling in a rabbit femoral defect model"; "comparison performance testing conducted in a rabbit critical size femoral defect model demonstrated equivalent bone formation and remodeling."
Overall Design/Labeling	Meets all requirements for overall design, sterilization, biocompatibility, labeling, and performance.	"Rafugen™ DBM meets all the requirements for overall design, sterilization, biocompatibility, labeling, and performance." (This is a summary statement, not a specific performance metric).
Shelf Life	Shelf life testing	Performed (mentioned as a conducted test, but specific results or acceptance criteria are not detailed beyond the implication that it passed).
Design Specifications	Meets design specifications and does not raise new questions of safety and effectiveness compared to predicate.	"The final composition of Rafugen™ DBM was found to be biocompatible and to meet its design specifications." "It has been shown in this 510(k) submission that the minor differences between the Rafugen™ DBM and the Grafton® DBM predicate device do not raise new questions regarding its safety and effectiveness."

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

The document mentions a "rabbit femoral condyle model" and a "rabbit critical size femoral defect model" for performance testing, and an "athymic rat assay (ectopic pouch model)" for osteoinductive potential. However, specific sample sizes (number of animals) for these animal studies are not provided in this 510(k) summary. The data provenance is pre-clinical animal studies, likely conducted by the manufacturer or contracted labs. There is no information about country of origin of the data provided. These are prospective studies in the sense that they were designed and executed to support the regulatory submission.

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

This information is not applicable as the document describes non-clinical (animal) studies, not studies involving human experts establishing ground truth for a diagnostic AI device.

4. Adjudication Method for the Test Set

This information is not applicable for the same reasons as point 3.

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

This information is not applicable as the device is a bone void filler, not an AI diagnostic tool that would involve multi-reader studies.

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

This information is not applicable as the device is a medical implant, not an AI algorithm.

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

For the animal studies:

Osteoinductive potential: The ground truth would be based on histological and/or imaging analysis of the ectopic bone formation in the athymic rat model, likely interpreted by scientific experts in the field.
Bone growth and remodeling: The ground truth would be based on histological, radiography, and/or micro-CT analysis of bone formation and remodeling within the rabbit femoral defect model, again interpreted by experts.

8. The sample size for the training set

This information is not applicable. The device is a manufactured medical product, not an AI algorithm that requires a training set. The "design specifications" and manufacturing processes are validated, not "trained."

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

This information is not applicable for the same reasons as point 8.

Summary

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Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the U.S. Food & Drug Administration (FDA). The Department of Health & Human Services logo is on the left, featuring a stylized human figure. The FDA logo is on the right, with the letters "FDA" in a blue square and the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

April 11, 2018

Cellumed Co., Ltd. % Justin Eggleton Senior Director. Spine Regulatory Affairs Musculoskeletal Clinical Regulatory Advisers, LLC 1050 K Street NW, Suite 1000 Washington, District of Columbia 20001

Re: K180121

Trade/Device Name: Rafugen™ 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 12, 2018 Received: January 16, 2018

Dear Mr. Eggleton:

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 forth in the quality systems (QS) regulation (21 CFR Part 820);

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Page 2 - Justin Eggleton

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 mediation-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,

Mark N. Melkerson -S

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

Enclosure

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Form Approved: OMB No. 0910-0120

Expiration Date: January 31, 2017

See PRA Statement below.

Indications for Use

510(k) Number (if known) K180121

Device Name Rafugen™ DBM

Indications for Use (Describe)

Rafugen DBM is intended for use as a bone void filler in bony voids or gaps of the skeletal system (i.e., pelvis and extremities) not intrinsic to the stability of the bony structure. The voids or gaps may be surgically created defects or defects created by traumatic injury to the bone. Rafugen DBM is resorbed/remodeled and is replaced by host bone during the healing process.

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:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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510(k) Summary (K180121)

for

Rafugen™ DBM

1. Submission Sponsor

Cellumed Co., Ltd. #402, 130, Digital-ro, Geumcheon-gu, Seoul Korea Phone: 82-2-2014-0475 Fax: 82-2-2104-0479 Contact: Joo Woong (Albert) Jang

2. Submission Correspondent

Justin Eggleton Senior Director, Spine Regulatory Affairs Musculoskeletal Clinical Regulatory Advisers, LLC 1050 K Street NW, Suite 1000 Washington, DC 20001 Email: jeggleton@mcra.com Phone: 202.552.5800

3. Date Prepared

April 4, 2018

4. Device Identification

Trade/Proprietary Name:	Rafugen™ DBM
Common/Usual Name:	Resorbable bone void filler containing demineralized bone
Classification Name:	Resorbable calcium salt bone void filler device
Classification Regulation:	21 CFR §888.3045
Product Code:	MBP, MQV
Device Class:	Class II
Classification Panel:	Orthopedic

5. Legally Marketed Predicate Device(s)

GRAFTON® DBM, K051195

6. Device Description

Rafugen™ DBM is a human bone allograft product containing human DBM (demineralized bone matrix), CMC (carboxymethyl cellulose), Starch and Glycerol. It is intended for use in

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filling bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure. Rafugen™ DBM is a ready-to use moldable gel formulation provided pre-filled in syringes of various volumes and is intended for single patient use. It is offered in six volumes: 0.25, 0.5, 1.0, 3.0, 5.0, and 10.0 cc. The Rafugen™ DBM can be either directly applied into the defect from the syringe, using the cap tip, or extruded for molding and insertion into the defect by hand.

Rafugen™ DBM is packaged in a double foil pouch and sealed within a PE pouch prior to placement into a paperboard carton.

7. Indication for Use Statement

8. Substantial Equivalence Discussion

The following table compares the Rafugen™ DBM to the predicate device with respect to intended use, technological characteristics and performance.

	Rafugen™ DBM	GRAFTON® DBMK051195	Comparison
Manufacturer	Cellumed Co., Ltd.	Osteotech Inc.	N/A
Classification Number	21 CFR §888.3045(Resorbable calcium saltbone void filer device)	21 CFR §888.3045(Resorbable calcium saltbone void filer device)	Same
Classification Product Code	MBP, MQV	MBP, MQV	Same
Indications for Use	Rafugen™ DBM is intendedfor use as a bone void fillerin bony voids or gaps of theskeletal system (i.e., pelvisand extremities) notintrinsic to the stability ofthe bony structure. Thevoids or gaps may besurgically created defects ordefects created bytraumatic injury to thebone. Rafugen™ DBM isresorbed/remodeled and isreplaced by host boneduring the healing process.	GRAFTON® DBM is intendedfor use as a bone graftextender, bone graftsubstitute, and bone voidfiller in bony voids or gapsof the skeletal system (i.e.,spine, pelvis andextremities) not intrinsic tothe stability of the bonystructure. The voids or gapsmay be surgically createddefects or defects createdby traumatic injury to thebone. GRAFTON® DBM isresorbed/remodeled and isreplaced by host boneduring the healing process.	Similar –GRAFTON® isalso indicatedfor use as abone graftextender andfor use in theposterolateralspine, whereasCellumed is notseeking thoseindications forRafugen™ DBM
Main Material	DBM, human cortical bonepowder	DBM, human cortical bonepowder	Same

Table 5A - Comparison of Characteristics

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Sub Material(Carrier)	CMC, Starch and Glycerol	Glycerol	Same forglycerol.(CMC and starchare additionalcarrier materialsto control theviscosity withglycerol)
Product Volume	0.25, 0.5, 1, 3, 5 and 10 cc	0.5, 1, 5 and 10 cc (Gelformat)	Similar —Rafugen™ DBMis also offered involumes of 0.25and 3 cc.
Format types	Gel type	Various, including Gel type	Same
Osteoinductivepotential	Yes, per athymic rat assay	Yes, per athymic rat assay	Same
Performance	Bone growth andremodeling in a rabbitfemoral defect model	Bone growth andremodeling in a rabbitfemoral defect model	Same – acomparisonstudy wasperformed byCellumed
Ready to use	Yes	Yes	Same
Presentation Type	Syringe	Syringe	Same(for Grafton®Gel)

Rafugen™ DBM is substantially equivalent to the predicate device with respect to materials in that it consists of human demineralized bone matrix (DBM) and an inert resorbable nontissue additive or carrier. The final composition of Rafugen™ DBM was found to be biocompatible and to meet its design specifications. The addition of starch and CMC to the formulation does not raise additional or different questions of safety and effectiveness.

GRAFTON® DBM is indicated for use as a bone graft extender and for use in the posterolateral spine, whereas Cellumed is not seeking those indications for Rafugen™ DBM. The narrower indication does not raise any additional questions of safety and effectiveness.

9. Non-Clinical Performance Data

As part of demonstrating safety and effectiveness of Rafugen™ DBM and in showing substantial equivalence to the predicate device, Cellumed completed a number of tests. In accordance with the "Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device,"June, 2003, the following testing has been performed to support substantial equivalence:

Chemical and physical properties ●
Biocompatibility ●
Sterility
furthermore Shelf Life
Comparison performance testing in rabbit femoral condyle model

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In addition, the device was tested for osteoinductive potential using an athymic rat assay (ectopic pouch model). Osteoinduction assay results using the athymic rodent assay should not be interpreted to predict clinical performance in human subjects.

Validation was performed for the Rafugen™ DBM processing to demonstrate inactivation of a panel of model viruses.

The device was tested for material mediated pyrogenicity. The test sample of Rafugen™ DBM was extracted in endotoxin free water, and evaluated by Endosafe" PTS™ system. Under the conditions of this study, no endotoxin level showed above 0.5 EU/mL in all five batches. The test extract was judged as non-pyrogenic, and the test sample satisfied the requirements for the absence of pyrogens.

Rafugen™ DBM meets all the requirements for overall design, sterilization, biocompatibility, labeling, and performance. The testing for osteoinductive potential of both devices was demonstrated using a validated athymic rat assay, and comparison performance testing conducted in a rabbit critical size femoral defect model demonstrated equivalent bone formation and remodeling.

10. Clinical Performance Data

There was no clinical testing required to support the medical device as the indications for use is equivalent to the predicate device. The non-clinical testing detailed in this submission supports the substantial equivalence of the device.

11. Statement of Substantial Equivalence

By definition, a device is substantially equivalent to a predicate device when the device has the same intended use and the same technological characteristics as the previously cleared predicate device, or the device has the same intended use and different technological characteristics, but it can be demonstrated that the new device does not raise different questions regarding its safety and effectiveness as compared to the predicate device as a result of the differences in technological characteristics.

It has been shown in this 510(k) submission that the minor differences between the Rafugen™ DBM and the Grafton® DBM predicate device do not raise new questions regarding its safety and effectiveness. The Rafugen™ DBM is therefore determined to be substantially equivalent to the predicate device.

12. Conclusion

The submitted 510(k) demonstrates Rafugen™ DBM is substantially equivalent to the predicate device.

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.