Rafugen DBM

K180121 · Cellumed Co., Ltd. · MQV · Apr 11, 2018 · Orthopedic

Device Facts

• Record ID: K180121
• Device Name: Rafugen DBM
• Applicant: Cellumed Co., Ltd.
• Product Code: MQV · Orthopedic
• Decision Date: Apr 11, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 888.3045
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

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 Story

Rafugen™ DBM is a human bone allograft bone void filler; composed of demineralized bone matrix (DBM), carboxymethyl cellulose (CMC), starch, and glycerol. Provided as a ready-to-use moldable gel in pre-filled syringes (0.25–10.0 cc). Applied directly into bony voids or gaps (pelvis/extremities) via syringe or manual molding. Intended for single-patient use. Device acts as a scaffold; resorbed and remodeled by host bone during healing. Used by surgeons in clinical settings to fill non-structural skeletal defects. Benefits include osteoinductive potential and biocompatible handling properties for bone repair.

Clinical Evidence

No clinical data. Substantial equivalence supported by non-clinical bench testing: chemical/physical property analysis, biocompatibility, sterility, shelf-life, and material-mediated pyrogenicity testing. Osteoinductive potential confirmed via athymic rat ectopic pouch model. Comparative performance (bone growth/remodeling) validated in a rabbit critical-size femoral defect model.

Technological Characteristics

Human DBM-based allograft; carrier includes CMC, starch, and glycerol. Form factor: moldable gel in pre-filled syringes. Sterilization: validated viral inactivation processing. Biocompatible, resorbable, and osteoinductive. No electronic components or software.

Indications for Use

Indicated for patients requiring bone void filling in the skeletal system (pelvis and extremities) for surgically created defects or traumatic injury; not for use in areas intrinsic to bony structure stability.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• GRAFTON® DBM (K051195)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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) |
|----------------------------------------------------------------------|
| <span> ☑ Prescription Use (Part 21 CFR 801 Subpart D) </span> |
| <span> ☐ Over-The-Counter Use (21 CFR 801 Subpart C) </span> |

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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: [phone] 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: [e-mail] Phone: [phone]

#### 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

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.

#### 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® DBM<br>K051195 | Comparison |
|-----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Manufacturer | Cellumed Co., Ltd. | Osteotech Inc. | N/A |
| Classification Number | 21 CFR §888.3045<br>(Resorbable calcium salt<br>bone void filer device) | 21 CFR §888.3045<br>(Resorbable calcium salt<br>bone void filer device) | Same |
| Classification Product Code | MBP, MQV | MBP, MQV | Same |
| Indications for Use | Rafugen™ DBM is intended<br>for use as a bone void filler<br>in bony voids or gaps of the<br>skeletal system (i.e., pelvis<br>and extremities) not<br>intrinsic to the stability of<br>the bony structure. The<br>voids or gaps may be<br>surgically created defects or<br>defects created by<br>traumatic injury to the<br>bone. Rafugen™ DBM is<br>resorbed/remodeled and is<br>replaced by host bone<br>during the healing process. | GRAFTON® DBM is intended<br>for use as a bone graft<br>extender, bone graft<br>substitute, and bone void<br>filler in bony voids or gaps<br>of the skeletal system (i.e.,<br>spine, pelvis and<br>extremities) not intrinsic to<br>the stability of the bony<br>structure. The voids or gaps<br>may be surgically created<br>defects or defects created<br>by traumatic injury to the<br>bone. GRAFTON® DBM is<br>resorbed/remodeled and is<br>replaced by host bone<br>during the healing process. | Similar –<br>GRAFTON® is<br>also indicated<br>for use as a<br>bone graft<br>extender and<br>for use in the<br>posterolateral<br>spine, whereas<br>Cellumed is not<br>seeking those<br>indications for<br>Rafugen™ DBM |
| Main Material | DBM, human cortical bone<br>powder | DBM, human cortical bone<br>powder | Same |

#### Table 5A - Comparison of Characteristics

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| Sub Material<br>(Carrier) | CMC, Starch and Glycerol | Glycerol | Same for<br>glycerol.<br>(CMC and starch<br>are additional<br>carrier materials<br>to control the<br>viscosity with<br>glycerol) |
|-----------------------------|-------------------------------------------------------------------|-------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------|
| Product Volume | 0.25, 0.5, 1, 3, 5 and 10 cc | 0.5, 1, 5 and 10 cc (Gel<br>format) | Similar —<br>Rafugen™ DBM<br>is also offered in<br>volumes of 0.25<br>and 3 cc. |
| Format types | Gel type | Various, including Gel type | Same |
| Osteoinductive<br>potential | Yes, per athymic rat assay | Yes, per athymic rat assay | Same |
| Performance | Bone growth and<br>remodeling in a rabbit<br>femoral defect model | Bone growth and<br>remodeling in a rabbit<br>femoral defect model | Same – a<br>comparison<br>study was<br>performed by<br>Cellumed |
| Ready to use | Yes | Yes | Same |
| Presentation Type | Syringe | Syringe | Same<br>(for Grafton®<br>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.