Grafton Plus® DBM Paste is intended for use as a bone graft extender, bone graft substitute, and bone void filler in bony voids or gaps of the skeletal system (i.e., spine, 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. Grafton Plus® DBM Paste is resorbed/remodeled and is replaced by host bone during the healing process.

Device Description

GRAFTON PLUS® DBM Paste is a human bone allograft product consisting of human demineralized bone matrix (DBM) to which an inert starch-based carrier has been added. It is intended for use in filling bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure. GRAFTON PLUS® DBM Paste is provided in a ready-to-use paste-like, malleable form that can be molded or manipulated by the user into various shapes. It is provided in various package sizes by volume. GRAFTON PLUS® DBM Paste is a demineralized bone product that is osteoconductive as well as osteoinductive in an athymic rat assay.

AI/ML Overview

The provided text describes the GRAFTON PLUS® DBM Paste, a demineralized bone matrix allograft. The study supporting its safety and effectiveness is primarily based on animal bone formation studies and the product's osteoinductive properties.

Here's an analysis of the acceptance criteria and study in relation to your requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Acceptance Criteria (as implied)	Reported Device Performance
Osteoinductivity	Consistent osteoinductivity in an athymic rat assay, using a 5-point linear scale (0-4) for bone formation at 28 days.	"validated to consistently produce DBM that is osteoinductive in an athymic rat assay." Achieved scores on a 5-point linear scale (0,1,2,3,4) for bone formation at 28 days.
Performance vs. Autograft	Comparable performance to autograft in bone formation.	"The results of bone formation studies in animals showed that GRAFTON PLUS® DBM Paste performed comparably to autograft."
Viral Inactivation	Validated inactivation of specified viruses (HIV-1, HBV, HCV, CMV, Polio virus) by the production process.	"proprietary production process that has been validated to inactivate viruses including: HIV-1; hepatitis B virus (duck hepatitis virus as model); hepatitis C virus (bovine diarrhea virus as model), CMV; and Polio virus."
Substantial Equivalence	Equivalence to predicate devices in material, form, and intended use.	Grafton Plus® DBM Paste is stated to be "substantially equivalent to one or more of the predicate devices with respect to materials in that it consists of human demineralized bone matrix (DBM) and an inert resorbable non-tissue additive or carrier. It is provided in a ready-to-use paste-like, malleable form that can be molded or manipulated by the user into various shapes."

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

Sample Size (Test Set): Not explicitly stated numbers for animals used in the bone formation studies. It mentions "ongoing testing" but not specific sample sizes for the "test set" in a traditional sense. The athymic rat assay is used for ongoing product and process consistency confirmation.
Data Provenance: Animal studies (athymic rat assay). No country of origin is specified for the animals. The studies are retrospective in the sense that the results are being reported after completion, but the "ongoing testing" suggests continuous evaluation.

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

Experts: Not explicitly stated within the provided text. The osteoinductivity assay uses a "five-point linear scale (0,1,2,3,4) to score bone formation." This implies expert scoring, but the number and qualifications are not detailed. The referenced publication (Edwards, J.T., PhD, Diegmann, M.H., MS, Scarborough, N.L., PhD) suggests that experts with relevant scientific backgrounds (PhD, MS) were involved in developing or executing the method.

4. Adjudication Method for the Test Set

Adjudication Method: Not explicitly stated. The use of a "five-point linear scale" suggests a standardized scoring method, but details on inter-rater reliability or adjudication of discrepancies are not provided.

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

MRMC Study: No. This device is a biomaterial (demineralized bone matrix paste), not an AI-powered diagnostic or assistive technology for human readers. Therefore, an MRMC study comparing human reader performance with and without AI assistance is not applicable.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Standalone Study: Yes, in an analogous sense for a device of this type. The performance of the GRAFTON PLUS® DBM Paste itself (e.g., its osteoinductive capacity, comparable performance to autograft) was evaluated directly in animal studies, without human intervention in the "performance" aspect of the paste. The scoring of the results (e.g., bone formation) would involve human observation and assessment, but the device's action is independent of a human-in-the-loop directly influencing its biological outcome.

7. The Type of Ground Truth Used

Ground Truth: In the context of bone formation:
- Expert Scoring/Histological Evaluation: The five-point linear scale for bone formation in the athymic rat assay heavily relies on expert assessment of tissue samples (histology).
- Comparative Performance: Comparison to "autograft" performance serves as a ground truth benchmark for effective bone healing. Autograft is often considered the gold standard for bone regeneration.

8. The Sample Size for the Training Set

Sample Size (Training Set): Not explicitly stated. The product is described as being prepared via a "proprietary processing method... that has been validated to consistently produce DBM that is osteoinductive." This validation process would implicitly involve a "training" or development phase to achieve consistency, but specific sample sizes for this phase are not provided in this summary.

9. How the Ground Truth for the Training Set Was Established

Ground Truth (Training Set): Implied through the "validation" of the proprietary processing method. The ground truth for the processing would be established by demonstrating that the resulting DBM consistently exhibits osteoinductivity as measured by the athymic rat assay (i.e., achieving specific scores on the 5-point scale). This would involve iterative testing and refinement of the processing method until the desired osteoinductive outcome is reliably achieved.

Summary

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NOV 2 3 2005

K043048

XII. 510(K) SUMMARY OF SAFETY AND EFFECTIVENESS

November 17, 2005

1. Submission Applicant & Correspondent:

Name:	Osteotech, Inc.
Address:	51 James WayEatontown, NJ 07724
Phone No.:	(732) 542-2800
Contact Person:	Chris Talbot

1. Name of Product:

Trade/Proprietary/Model Name:	GRAFTON PLUS® DBM Paste
Common or Usual Name:	Demineralized Bone Matrix Allograft
Classification Name:	Resorbable Bone Void Filler

1. Devices to Which New Product is Substantially Equivalent:
  GRAFTON PLUS® DBM Paste is substantially equivalent, for the purpose of this 510(k), to the following predicate devices.

Trade/Proprietary/Model Name	Manufacturer	510(K) #
Exactech Resorbable Bone Paste	Exactech	K020078
Exactech Resorbable RoomTemperature Bone Paste	Exactech	K040755
Allomatrix Putty	Wright Medical	K020895
Allomatrix Putty	Wright Medical	K041186

1. Device Description:
  GRAFTON PLUS® DBM Paste is a human bone allograft product consisting of human demineralized bone matrix (DBM) to which an inert starch-based carrier has been added. It is intended for use in filling bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure. GRAFTON PLUS® DBM Paste is provided in a ready-to-use paste-like, malleable form that can be molded or manipulated by the user into various shapes. It is provided in various package sizes by volume.

GRAFTON PLUS® DBM Paste is a demineralized bone product that is osteoconductive as well as osteoinductive in an athymic rat assay. It is prepared via a proprietary processing method of Osteotech, Inc. that has been validated to consistently produce DBM that is osteoinductive in an athymic rat assay. Product and process consistency are confirmed via ongoing testing of GRAFTON PLUS® DBM Paste finished product for osteoinductivity in this

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validated athymic rat assay utilizing a five-point linear scale (0,1,2,3,4) to score bone formation at 28 days*. This bone forming activity exhibited by GRAFTON PLUS® DBM Paste in this athymic rat surrogate assay should not be interpreted as a predictor of clinical performance.

*Edwards, J.T., PhD, Diegmann, M.H., MS, Scarborough, N.L., PhD .: Osteoinduction of Human Demineralized Bone: Characterization in a Rat Model. Clinical Orthopaedics, December, 1998. Volume 357.

5. Intended Use/Indications

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

1. Technical Comparison
  Grafton Plus® DBM Paste is substantially equivalent to one or more of the predicate devices with respect to materials in that it consists of human demineralized bone matrix (DBM) and an inert resorbable non-tissue additive or carrier. It is provided in a ready-to-use paste-like, malleable form that can be molded or manipulated by the user into various shapes.

7. Performance Data

The results of bone formation studies in animals showed that GRAFTON PLUS® DBM Paste performed comparably to autograft. Additional relevant animal and clinical data exist that support the performance of GRAFTON PLUS® DBM Paste.

8. Viral Inactivation

GRAFTON PLUS® DBM Paste is produced by a proprietary production process that has been validated to inactivate viruses including: HIV-1; hepatitis B virus (duck hepatitis virus as model); hepatitis C virus (bovine diarrhea virus as model), CMV; and Polio virus. This process is used to further reduce the risk of disease transmission via the use of this product beyond the protection provided by donor testing and screening procedures.

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Public Health Service

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

NOV 2 3 2005

Mr. Christopher Talbot Director, Regulatory Affairs Osteotech, Inc. 51 James Way Eatontown, NJ 07724

Re: K043048

GRAFTON PLUS® DBM Paste Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler devices Regulatory Class: Class II Product Code: MBP Dated: November 10, 2005 Received: November 14, 2005

Dear Mr. Talbot:

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.

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Page 2 - Mr. Christopher Talbot

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.

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 (240) 276-0120. 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 (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Mark N. 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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Indications for Use - Statement III.

K043048 510(k) Number (if known):_____________________________________________________________________________________________________________________________________________________

Device Name: GRAFTON PLUS® DBM Paste

Indications for Use:

Grafton Plus® DBM Paste is intended for use as a bone graft extender, bone graft substitute, and bone void filler in bony voids or gaps of the skeletal system grant babothates) and extremities) not intrinsic to the stability of the bony structure. The voids or gaps may be surgically created defects or defects strated by traumatic injury to the bone. Grafton Plus® DBM Paste is oreatou by tradmatic injury replaced by host bone during the healing process.

Prescription Use × (Per 21 CFR 801.109) OR

Over-The-Counter Use (Optional Format 1-2-96)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off) Division of General, Restorative, and Neurological Devices

510(k) Number_KO43048

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.