DYNAGRAFT II

K040419 · Isotis Orthobiologics, Inc. · MQV · Mar 25, 2005 · Orthopedic

Device Facts

• Record ID: K040419
• Device Name: DYNAGRAFT II
• Applicant: Isotis Orthobiologics, Inc.
• Product Code: MQV · Orthopedic
• Decision Date: Mar 25, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 888.3045
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

For orthopedic applications as filler for gaps or voids that are not intrinsic to the stability of the bony structure. DynaGraft II is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender (extremities, spine, and pelvis) and as bony void filler of the extremities and pelvis. These defects may be surgically created or the result of traumatic injury to the bone.

Device Story

DynaGraft II is a bone void filler composed of demineralized bone matrix (DBM) derived from donated human tissue, combined with a polyethylene oxide/polypropylene oxide block copolymer carrier. The carrier exhibits reverse phase characteristics, increasing in viscosity as temperature rises. The device is provided sterile for single-patient use. It is intended for orthopedic applications, specifically as a bone graft extender or void filler in the extremities, spine, and pelvis. Surgeons pack the gel or putty into bony gaps resulting from trauma or surgery. The device acts as an osteoconductive scaffold to support new bone ingrowth. Clinical benefit is derived from its ability to fill voids and facilitate bone repair in the skeletal system.

Clinical Evidence

Bench testing included viral inactivation validation using a panel of viruses and an in vitro assay measuring alkaline phosphatase activity in myoblast cells to confirm osteoinductive potential, validated against an in vivo athymic rat muscle pouch model. Product performance was evaluated in rabbit and sheep models using radiographic and histological methods. Clinical studies in spine applications reported acceptable outcomes.

Technological Characteristics

Resorbable bone void filler. Materials: Demineralized bone matrix (DBM) and polyethylene oxide/polypropylene oxide block copolymer carrier. Form factor: Gel or putty. Principle: Osteoconductive scaffold. Sterilization: Sterile. Connectivity: None.

Indications for Use

Indicated for patients requiring bone graft extension or void filling in the extremities, spine, and pelvis. Used for surgically created or traumatic bone defects. Not for use in areas where the defect is intrinsic to the stability of the bony structure.

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

• AlloMatrix DBM Putty with inert carrier Sodium Carboxymethylcellulouse (K040980)
• InterGro DBM with inert carrier Lecithin (K031399)

Submission Summary (Full Text)

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K040419

## 510(k) Summary

# lsoTis OrthoBiologics DynaGraft II

#### Sponsor 1.

IsoTis OrthoBiologics, Inc. 2 Goodyear, Suite B Irvine, CA 92618 U.S.A

| Contact Person: | Paul Doner |
|-----------------|--------------|
| Telephone: | 949 855-7168 |
| Facsimile: | 949 595-8711 |

March 2005 Date Prepared:

#### Device Name 2.

| Proprietary Name: | DynaGraft II Gel and Putty |
|----------------------|----------------------------------------------------------------|
| Common/Usual Name: | Bone Void Filler |
| Classification Name: | Sec. 888.3045 Resorbable calcium salt bone void filler device. |

#### Predicate Devices 3.

AlloMatrix ® DBM Putty with inert carrier Sodium Carboxymethylcellulouse (K040980) InterGro® DBM with inert carrier Lecithin (K031399)

#### Device Description 4.

DynaGraft II is derived from selected donated human bone tissue that has been DynaGrait if is defived from selociosations are subsequently demineralized using a processed into partier. The demineralized bone matrix (DBM) is combined with nydroomono actu prise carrier and formulated to a gel or putty-like consistency.

The carrier is a solution of polyethylene oxide polypropylene oxide block copolymer The ourner to a colutibiting reverse phase characteristics (i.e., an increase in viscosity as temperature increases).

#### Intended Use 5.

For orthopedic applications as filler for gaps or voids that are not intrinsic to the r of or the bony structure. DynaGraft II is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender (extremities, spine, and pelvis) gaps in the extremities and pelvis. These defects may belvis. These defects may be surgically created or the result of traumatic injury to the bone.

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### Technological Characteristics and Substantial Equivalence 6.

DynaGraft II and its predicate devices are similar in design, materials of construction DynaOration. The proposed and predicate devices are osteoconductive and and function. The proposed afta product and its predicate devices provide an Usteomductive. The Dynachat if in the environment for new bone ingrowth and intereofineoted, porode seemed are provided sterile and for single patient use. Stimulate bono growin. We proposed device and its predicates are the inert The only difference betwoon the proposed areaft II product meets the requirements of can for about safety and effectiveness is adequately supported by the the AATD. Troduct outsity and tion, materials data, and test results provided in this Premarket Notification.

- Viral Inactivation Validation -
The methods for processing the DBM contained in DynaGraft II were evaluated for their viral inactivation potential. A select panel of viruses representing various virus types, sizes, shapes, and genomes were evaluated. The viral inactivation testing demonstrated suitable viral inactivation potential of the processing methods for a wide range of potential human viruses.

- Osteoinductivety Potential
The osteoinductive potential of the DBM used in DynaGraft II is determined via an in vitro assay The assay measures the alkaline phosphatase activity of myoblast cells. The level of alkaline phosphatese induction is compared to positive and negative DBM controls. Results from the assay were correlated with results from implantation of DBM into an athymic rat muscle pouch. Analysis of these results shows that the in vitro assay has been validated against the in vivo athymic rat model and predicts with at least 95% confidence the in vivo osteoinductivity of the test material. 67 out of 67 test lots that passed the in vitro assay passed the in vivo athymic rat assay via confirmation of intramuscular bone formation.

Each lot of DBM incorporated in the DynaGraft II is evaluated for osteoinductive potential using an in vitro assay. Testing each lot of DBM assures that only DBM with ostoeinductive potential is used in DynaGraft II. Although DBM used in the final product has been shown to be osteoinductive using an in vitro assay, the combination of DBM and inert carrier has not been evaluated for osteoinductivity; therefore, it is unknown to what extent the formulation components may alter the osteoinductivity character of the DBM. Additionally, it is unknown how osteoinductivity of the DBM component, measured via the in vitro assay, will correlate with human clinical performance of DynaGraft II.

Product Performance Testing Performance of DynaGraft II DBM has been evaluated in rabbit and sheep models by radiographic and histological methods for the indications specified in the Premarket Notification.

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Clinical studies using DynaGraft II DBM Putty and Gel have been performed Olinioal studios deing of the spintrating acceptable outcomes.

These data substantiate DynaGraft II Putty and Gel safety and effectiveness for the indications presented in this Premarket Notification.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird with three stylized wing shapes.

Public Health Service

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

MAR 2 5 2005

Mr. Paul Donor Director of Quality Assurance and Regulatory Affairs IsoTis Orthobiologics, Inc. 2 Goodyear Irvine, CA 92618

Re: K040419

DynaGraft II Gel and DynaGraft II Putty Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler devices Regulatory Class: Class II Product Code: MQV Dated: January 5, 2005 Received: January 7, 2005

Dear Mr. Doner:

We have reviewed your Section 510(k) premarket notification of intent to market the device indication we have reviewed your Section 910(x) premaine is substantially equivalent (for the indications
referenced above and have determined the device is substantial in interests a referenced above and nave determined the actived predicate devices marketed in interstate for use stated in the encrosule) to regally manatise provice Americal Device Ameridments, or to commerce prior to May 28, 1776, the characters and of the Federal Food, Drug, devices that have been reclassified in accordance was a premarket approval application (PMA).
and Cosmetic Act (Act) that do not require approval of a premarket approval appl and Cosment Act (Act) that do not require approvinces of the general controls provisions of the Act. The You may, therefore, market the device, bacyce recurements for annual registration, listing of general controls provisions of the rise labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), in if your device is classifica (see above) into existing major regulations affecting your device can
may be subject to such additional controls. Existing major may be subject to such adultional controlis. Extrong stage of the 21, In addition, FDA may be found in the Code of Pouch oncerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean Prease be advised that FDA s issualled of a budenies with other requirements of the Act that IDA has made a determination in administered by other Federal agencies. You must of any rederal statutes and regulations and limited to: registration and listing (21 comply with an the Act 3 requirements, movements.
CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set

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Page 2 - Mr. Paul Donor

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic form in the quant) of evelsions (Sections 531-542 of the Act); 21 CFR 1000-1050. product radiation control provisions (reting your device as described in your Section 510(k) I mis lotter will and in yours finding of substantial equivalence of your device to a legally premaince notification " Tresults in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please n you desire of Compliance at [phone]. Also, please note the regulation entitled, Connect the Ories of Course to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small other gotterers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Stypk Plurke

Mirian C. Provost, Ph.D. Acting Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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K040419 510(k) Number (if known):

Device Name: DynaGraft® II Gel and Putty

Indications for Use:

DynaGraft® II is indicated for orthopedic applications as filler for gaps or voids that are DynaGratt' II is indicated for orthopedically as mar roll gadicated to be packed to be packed to be packed not intrinsic to the stablity of the bony strate. Dyne graft extender (extremities, spine,
gently into bony gaps in the skeletal system as a bone graft extremities, spine, gently into bony gaps in the skeletal System as a some of these defects may be pervis) and as bony vold fillor of the extrainatic injury to the bone.

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801 Subpart D)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ AND/OR

(Per 21 CFR 801 Subpart C)

### PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NECESSARY)

# Concurrence of CDRH, Office of Device Evaluation (ODE)

Styke Reurke

Division of General, Restorative, and Neurological Devices

510(k) Number_________________________________________________________________________________________________________________________________________________________________