CONNEXUS, .5CC, MODEL 023000-005

K052098 · Isotis Orthobiologics, Inc. · MQV · Sep 7, 2005 · Orthopedic

Device Facts

• Record ID: K052098
• Device Name: CONNEXUS, .5CC, MODEL 023000-005
• Applicant: Isotis Orthobiologics, Inc.
• Product Code: MQV · Orthopedic
• Decision Date: Sep 7, 2005
• Decision: SESE
• Submission Type: Special
• 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. Connexus is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender and as a bone void filler of the extremities and pelvis. These defects may be surgically created or the result of traumatic injury to the bone.

Device Story

Connexus is a bone void filler composed of demineralized bone matrix (DBM) particles derived from human donor tissue, combined with an inert reverse-phase carrier (polyethylene oxide polypropylene oxide block copolymer in water). The carrier exhibits temperature-dependent viscosity, increasing as temperature rises to maintain a putty-like consistency. The device is intended for surgical use by physicians to fill non-structural bony gaps in the extremities and pelvis. It acts as an osteoconductive and osteoinductive scaffold, providing an environment for new bone ingrowth. The device is provided sterile for single-patient use. Clinical benefit is derived from its ability to serve as a bone graft extender in orthopedic procedures.

Clinical Evidence

No human clinical trials provided. Evidence includes bench testing (viral inactivation validation), in vitro osteoinductivity assays (alkaline phosphatase activity in myoblast cells), and animal studies (rabbit and sheep models) using radiographic and histological evaluation. In vitro assay validated against in vivo athymic rat muscle pouch model (67/67 lots passed).

Technological Characteristics

Materials: Demineralized human bone matrix, polyethylene oxide polypropylene oxide block copolymer carrier. Form: Putty. Sterilization: Radiation (ISO 11137). Standards: ISO 10993-1 (biocompatibility), ASTM 1980-02 (accelerated aging), 21 CFR 1270, AATB standards. Connectivity: None. Energy: None.

Indications for Use

Indicated for orthopedic patients requiring bone void filling in extremities and pelvis; for gaps/voids not intrinsic to bony stability; defects may be surgically created or traumatic. Contraindicated for use in load-bearing applications.

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

• Connexus (K050690)

Submission Summary (Full Text)

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K 052098

# 510(k) Summary of Safety and Effectiveness 1.4

## 1. Sponsor

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 |

Date Prepared: August 2, 2005

## 2. Device Name

| Proprietary Name: | Connexus, 0.5cc |
|----------------------|-------------------------------------------------------------------|
| Common/Usual Name: | Bone Void Filler |
| Classification Name: | Sec. 888.3045 Resorbable calcium salt bone void filler<br>device. |

## 3. Predicate Devices

Connexus (K050690, July 7, 2005)

## 4. Device Description

IsoTis OrthoBiologics is expanding the range of sizes previously cleared in 510(k) K050690 to include Connexus, 0.5cc. The intended use of this additional size does not change from that previously cleared.

Connexus is derived from selected donated human bone tissue that has been processed into particles. The bone particles are subsequently demineralized using a hydrochloric acid process. The demineralized bone matrix (DBM) is combined with an inert reverse phase carrier and formulated to a putty-like consistency.

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

# 5. Intended Use

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

#### Technological Characteristics and Substantial Equivalence 6.

Connexus and its predicate devices are similar in design, materials of construction and function. The proposed and predicate devices are osteoconductive and osteoinductive. The Connexus product and its predicate devices provide an interconnected, porous scaffold and an environment for new bone ingrowth and stimulate bone growth. The only differences between the proposed device and its predicates are the percentage of demineralized bone and the inert carriers used. Connexus is provided sterile and for single patient use. The donor bone in the Connexus product meets the requirements of the AATB. Product safety and effectiveness is adequately supported by the substantial

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equivalence information, materials data, and test results provided in this Premarket Notification.

- Viral Inactivation Validation -
The methods for processing the DBM contained in Connexus 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.

- Osteoinductivity Potential
The osteoinductive potential of the DBM used in Connexus 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 Connexus 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 Connexus. 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 Connexus.

# Product Performance Testing

Performance of Connexus has been evaluated in rabbit and sheep models by radiographic and histological methods for the indications specified in the Premarket Notification.

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

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# 1.5 Performance Standards

No performance standards applicable to Connexus bone void filler material have been adopted under Section 514 of the Act. Connexus complies where appropriate with the applicable requirement of the following voluntary/consensus standards:

- ISO 10993-1: Biological Evaluation of Medical Devices Part-1: Evaluation and Testing .
- . 21 CFR 1270, Human Tissue Intended for Transplantation
- . United States Pharmacopeia (USP) XXVI - The National Formulary (NF) Specifications XXI
- . United States Pharmacopeia (USP) XXVII - The National Formulary (NF) Specifications XXII
- . ISO 11137:1997; Sterilization of Health Care Products – Requirements for Validation and Routine Control - Radiation Sterilization
- . ASTM 1980 – 02:1999 (current edition approved Jan. 2002); Standard Guide for Accelerated Aging of Sterile Medical Device Packages
- American Association Standards for Tissue Banking, (10" Edition printing date: April . 2002)

Additionally, IsoTis OrthoBiologics' Quality System complies with the FDA Quality System Requirements (21 CFR 820), ISO 13485 and its facility is American Association of Tissue Banks (AATB) accredited.

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SEP - 7 2005

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. Paul Doner Director of Regulatory Affairs and Quality Assurance IsoTis OthoBiologics Inc. 2 Goodyear, Suite B Irvine, California 92618

Re: K052098 Trade Name: Connexus™, 0.5cc Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: II Product Code: MQV Dated: August 2, 2005 Received: August 11, 2005

Dear Mr. Doner:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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); 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. Paul Doner

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results 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 contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

*Mali A-McMillan*

Mark Melkerson Acting Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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# Statement of Indications for Use 1.3

510(k) Number (if known):

Device Name:

Connexus ™, 0.5cc

Indications for Use:

Connexus is an osteoinductive and osteoconductive bone filiing material indicated:

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

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (Part 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)

Mark A. Mckinnon

(Division Sign-( Division of General. Sestorative, and Neurologica

510(k) Number