GRAFTON® DBM is intended to be packed into bony voids or gaps to fill and/or augment dental intraosseous, oral and cranio-/maxillofacial defects. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone, including periodontal/infrabony defects; alveolar ridge augmentation (sinusotomy, osteotomy, cystectomy); dental extraction sites (ridge maintenance, implant preparation/placement); sinus lifts; cystic defects; craniofacial augmentation. GRAFTON® DBM may be used alone in a manner comparable to autogenous bone chips or allograft bone particulate (demineralized freeze dried bone), or it may be mixed with either allograft or autograft bone or bone marrow as a bone graft extender. GRAFTON® DBM is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. GRAFTON® DBM is resorbed/remodeled and is replaced by host bone during the healing process.

Device Description

GRAFTON® DBM is a human bone allograft product containing human demineralized bone matrix (DBM) and an inert additive for intraoperative handling. It is intended to fill and/or augment dental intraosseous, oral and cranio-/maxillofacial defects. GRAFTON® DBM is provided ready-to-use in various physical forms. It is packaged in various sizes by volume or dimension for single patient use. GRAFTON® DBM 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.

AI/ML Overview

This document describes a 510(k) premarket notification for the GRAFTON® DBM (Demineralized Bone Matrix) product. As such, it is not a study proving device meets acceptance criteria in the sense of a clinical trial for a novel AI device. Instead, it is a submission demonstrating substantial equivalence to legally marketed predicate devices, which is a different regulatory pathway.

Therefore, many of the typical questions regarding acceptance criteria, performance studies, sample sizes, expert ground truth, and comparative effectiveness for AI devices are not applicable in this context. The document focuses on demonstrating that GRAFTON® DBM is as safe and effective as existing devices.

However, I can extract the relevant information from the provided text based on the closest applicable concepts:

1. Table of Acceptance Criteria and Reported Device Performance

For a 510(k) submission, "acceptance criteria" are generally related to demonstrating substantial equivalence to predicate devices, focusing on materials, intended use, and performance characteristics (like osteoinductivity for DBM products). "Reported device performance" for DBMs typically refers to their biological properties.

Acceptance Criterion (Implicit for DBM)	Reported Device Performance (GRAFTON® DBM)
Material Composition (Substantial Equivalence)	Contains human demineralized bone matrix (DBM) in a resorbable non-tissue additive or carrier, substantially equivalent to predicate devices.
Intended Use/Indications (Substantial Equivalence)	Intended to fill and/or augment dental intraosseous, oral and cranio-/maxillofacial defects, consistent with predicate devices.
Osteoconductivity	Osteoconductive.
Osteoinductivity	Osteoinductive in an athymic rat assay. The proprietary processing method is validated to consistently produce osteoinductive DBM. Bone formation is scored on a five-point linear scale (0-4) at 28 days*.
Viral Inactivation	Proprietary production process validated to inactivate viruses including HIV-1, hepatitis B, hepatitis C, CMV, and Polio virus, further reducing disease transmission risk beyond donor screening.
Overall Performance (compared to predicates/alternatives)	The results of studies in animals and humans show that GRAFTON® DBM performs at least as well as, if not better than, predicate devices, autograft and/or demineralized bone matrix. (Note: Specific study details are not provided in this summary but are referenced as existing.)

*Note on : The document explicitly states: "This bone forming activity exhibited by GRAFTON® DBM in this athymic rat surrogate assay should not be interpreted as a predictor of clinical performance." This highlights that while the assay demonstrates a biological characteristic, it's not a direct measure of clinical success.

2. Sample size used for the test set and the data provenance

For the osteoinductivity assay:

Sample size: Not explicitly stated, but the method describes "ongoing testing of GRAFTON® DBM finished product for osteoinductivity in this validated athymic rat assay". This suggests a continuous testing process rather than a single fixed "test set" in the context of a clinical trial.
Data provenance: Athymic rat model. This is an animal model, not human data. The specific country of origin is not mentioned, but the associated reference (Edwards et al., 1998) suggests US-based research. Retrospective/prospective is not directly applicable to an ongoing assay of a manufactured product.

For the statement "results of studies in animals and humans show that GRAFTON® DBM performs at least as well as...":

Sample size: Not specified in this 510(k) summary. These would refer to existing, presumably published or unpublished, studies.
Data provenance: Mention of "animals and humans" but no further detail on country of origin or retrospective/prospective nature.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

For the athymic rat assay: Ground truth (scoring of bone formation) would typically be established by trained laboratory personnel or pathologists specializing in histology. The number of experts and their specific qualifications are not detailed in this summary. The mention of a "five-point linear scale (0,1,2,3,4) to score bone formation" suggests a standardized, objective scoring method.

4. Adjudication method for the test set

Not specified for the athymic rat assay, nor is it explicitly mentioned for any 'test set' in the context of a human clinical study. Given the nature of a 510(k) summary and the animal model, a formal multi-reader adjudication method as seen in complex clinical imaging trials is unlikely to be detailed here.

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

No. This document describes a medical device (bone graft material), not an AI-powered diagnostic or assistive technology. Therefore, an MRMC study comparing human readers with and without AI assistance is not applicable and was not performed.

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

No. This is a medical device, not an algorithm. This question is not applicable.

7. The type of ground truth used

For the osteoinductivity evaluation: Histological assessment (scoring of bone formation on a five-point scale) in an athymic rat model, based on a validated assay. This is a surrogate marker for human clinical performance.
For the broader claim of performing "at least as well as" predicates: This would implicitly rely on clinical outcomes data (e.g., fusion rates, healing rates) from animal and human studies, though specific details are not provided in this summary.

8. The sample size for the training set

This concept is not applicable in the context of a 510(k) for a DBM product. There is no "training set" for an algorithm. The "proprietary processing method" is validated to consistently produce osteoinductive DBM, which implies quality control and process validation, not machine learning model training.

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

This question is not applicable for the reasons stated in point 8. The "ground truth" for ensuring consistent product quality (i.e., osteoinductivity) is established through the validated athymic rat assay as described in point 7.

Summary

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XII. 510(K) SUMMARY OF SAFETY AND EFFECTIVENESS

December 16, 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® DBM (Gel, Flex, Putty, Matrix, Crunch)
Common or Usual Name:	Demineralized Bone Matrix Allograft
Classification Name:	Bone Grafting Material

1. Devices to Which New Product is Substantially Equivalent:
  GRAFTON® DBM is substantially equivalent, for the purpose of this 510(k), to other devices that have received 510(k) clearance for similar indications for use.

In addition, GRAFTON® DBM is substantially equivalent to human freeze dried bone, such as demineralized bone matrix, to which one or more predicate devices in this device category have claimed substantial equivalence.

1. Device Description:
  GRAFTON® DBM is a human bone allograft product containing human demineralized bone matrix (DBM) and an inert additive for intraoperative handling. It is intended to fill and/or augment dental intraosseous, oral and cranio-/maxillofacial defects. GRAFTON® DBM is provided ready-to-use in various physical forms. It is packaged in various sizes by volume or dimension for single patient use.

GRAFTON® DBM 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® DBM finished product for osteoinductivity in this validated athymic rat assay utilizing a

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five-point linear scale (0,1,2,3,4) to score bone formation at 28 days*. This bone forming activity exhibited by GRAFTON® DBM 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

6. Technical Comparison

GRAFTON® DBM is substantially equivalent to one or more of the predicate devices with respect to materials in that it contains human demineralized hone matrix (DBM) in a resorbable non-tissue additive or carrier. It is provided readyto-use in various malleable/flexible forms that can be molded, manipulated on cut by the user into various shapes or sizes. It is implanted in this malleable/flexible state.

7. Performance Data

The results of studies in animals and humans show that GRAFTON® DBM performs at least as well as, if not better than, predicate devices, autograft and/or demineralized bone matrix. Additional relevant animal and clinical data exist that support the successful performance of GRAFTON® DBM.

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8. Viral Inactivation

GRAFTON® DBM 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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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an emblem of an eagle with its wings spread.

Public Health Service

2006 JAN 3

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. Christopher Talbot Director, Regulatory Affairs Osteotech, Incorporated 51 James Way Eatontown, New Jersey 07724

Re: K051188

Trade/Device Name: GRAFTON® DBM Regulation Number: 872.3930 Regulation Name: Bone Grafting Material Regulatory Class: II Product Code: NUN Dated: December 19, 2005 Received: December 20, 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.

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Page 2 – Mr. Talbot

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 (OS) 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) 276-0115. 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,

Chiu-Lin, Ph.D.

Chiu Lin, Ph.D. Director Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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K051188

Indications for Use - Statement 111.

510(k) Number (if known):_____________________________________________________________________________________________________________________________________________________

Device Name: GRAFTON® DBM

Indications for Use:

GRAFTON® DBM is intended to be packed into bony voids or gaps to fill and/or augment dental intraosseous, oral and cranio-/maxillofacial defects. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone, including periodontal/infrabony defects; alveolar ridge augmentation (sinusotomy, osteotomy, cystectomy); dental extraction sites (ridge maintenance, implant preparation/placement); sinus lifts: cystic defects: craniofacial augmentation. GRAFTON® DBM may be used alone in a manner comparable to autogenous bone chips or allograft bone particulate (demineralized freeze dried bone), or it may be mixed with either allograft or autograft bone or bone marrow as a bone graft extender. GRAFTON® DBM is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. GRAFTON® DBM is absorbed/remodeled and replaced by host bone during the healing process.

Prescription Use X (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)

Susan Pearson

KOS 1182

Regulation Number and Section

§ 872.3930 Bone grafting material.

(a)
Identification. Bone grafting material is a material such as hydroxyapatite, tricalcium phosphate, polylactic and polyglycolic acids, or collagen, that is intended to fill, augment, or reconstruct periodontal or bony defects of the oral and maxillofacial region.(b)
Classification. (1) Class II (special controls) for bone grafting materials that do not contain a drug that is a therapeutic biologic. The special control is FDA's “Class II Special Controls Guidance Document: Dental Bone Grafting Material Devices.” (See § 872.1(e) for the availability of this guidance document.)(2) Class III (premarket approval) for bone grafting materials that contain a drug that is a therapeutic biologic. Bone grafting materials that contain a drug that is a therapeutic biologic, such as biological response modifiers, require premarket approval.
(c)
Date premarket approval application (PMA) or notice of product development protocol (PDP) is required. Devices described in paragraph (b)(2) of this section shall have an approved PMA or a declared completed PDP in effect before being placed in commercial distribution.