PROGENIX® DBM Putty and PROGENIX® Plus are intended for the augmentation of deficient maxillary and mandibular alveolar ridges and the treatment of oralmaxillofacial and dental intraosseous defects including but not limited to:

Ridge augmentation

Filling of cystic defect

Filling of extraction sites

Filling of lesions of periodontal origin

Craniofacial augmentation

Filling of defects of endodontic origin

Mandibular reconstruction

Repair of traumatic defects of the alveolar ridge, excluding maxillary and mandibular fracture

Filling of resection defects in benign bone tumors, benign cysts or other osseous defects in the alveolar ridge wall.

Device Description

PROGENIX® contains human demineralized bone matrix (DBM) in a biocompatible carrier. The carrier is a mixture of bovine collagen with a natural polysaccharide (sodium alginate). The components are mixed in phosphate buffered saline to achieve a flowable or moldable consistency. PROGENIX® is available in two forms: Putty and Plus. The PROGENIX® Plus version contains two different sized demineralized bone particles.

PROGENIX® DBM Putty and PROGENIX® Plus are single use products intended for use in the oralmaxillofacial region. Additionally, these products are not designed to impart any mechanical strength to the surgical site. Both versions are provided in ready-to-use malleable forms that may be molded or manipulated by the surgeon into various shapes. These products have been shown to be osteoinductive in an athymic rat assay, as well as osteoconductive, allowing for bony ingrowth across the graft site while resorbing at a rate consistent with bony healing.

AI/ML Overview

The provided text is a 510(k) summary for a medical device called PROGENIX® Plus, a resorbable calcium salt bone void filler device. It is a Special 510(k) for a device modification, seeking to include a new formulation to an already cleared product line. The primary goal is to demonstrate substantial equivalence to predicate devices, not necessarily to prove a specific level of performance against quantitative acceptance criteria through a clinical study.

Therefore, the information typically requested in your template (e.g., sample sizes for test/training sets, expert qualifications, MRMC studies, standalone performance, specific ground truth types) is largely not applicable in this context, as a clinical study with such detailed parameters was not conducted or required for this type of submission.

Instead, the "acceptance criteria" and "study" are focused on demonstrating the osteoinductive potential and viral inactivation effectiveness of the product, primarily through non-clinical testing, and showing substantial equivalence to existing devices.

Here's a breakdown based on the available information:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance (or Demonstration)
Osteoinductivity Potential: All DBM (Demineralized Bone Matrix) used must induce bone formation when evaluated in a validated athymic nude rat assay. Raw material and final product screening must show histologic evidence of osteoinduction through the presence of osteoblasts, chondroblasts, and/or woven bone.	PROGENIX® Plus demonstrates histologic evidence of osteoinduction (presence of osteoblasts, chondroblasts, and/or woven bone) in the athymic nude rat assay. (This is implied by the statement that it "must induce bone formation" and the product being cleared).
Viral Inactivation: The processing steps for tissue and collagen must be validated to inactivate a panel of clinically relevant viruses. The cortical bone processing and additional DBM steps must demonstrate effectiveness in inactivating viruses.	The processing steps for PROGENIX® Plus are validated to inactivate a panel of viruses, and further steps demonstrate suitable viral inactivation potential for a wide range of potential human viruses.
Substantial Equivalence: The modified device (PROGENIX® Plus) must be substantially equivalent to previously cleared predicate devices for its intended use and technological characteristics.	The FDA deemed PROGENIX® Plus substantially equivalent to PROGENIX® DBM Putty (K080462) and GRAFTON® DBM Crunch (K051188).

Study Details

Given the nature of a 510(k) for a bone void filler, the "studies" refer to non-clinical tests rather than human clinical trials involving extensive statistical analysis of human performance.

Sample size used for the test set and the data provenance:
- Osteoinductivity Assay: The sample size would refer to the number of athymic nude rats used in the in vivo assay. This information is not provided in the summary.
- Viral Inactivation: Not applicable in terms of a "test set" like a clinical study. It refers to in vitro validation studies on the manufacturing process.
- Data Provenance: Not explicitly stated, but typically these non-clinical studies are conducted in a controlled laboratory environment (e.g., manufacturer's labs or contract research organizations), likely in the country of manufacture (USA for Medtronic Sofamor Danek). All data would be prospective for the purpose of validating the new formulation.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Osteoinductivity Assay: The "ground truth" for osteoinductivity would be established by histopathological evaluation of the rat tissue. The number and qualifications of the pathologists or histologists performing this evaluation are not provided.
- Viral Inactivation: The ground truth is based on established virology assays to quantify viral reduction. The experts would be virologists and microbiologists within the testing facility. This information is not provided.
Adjudication method for the test set:
- Osteoinductivity Assay: Adjudication methods for histological evaluation (e.g., multiple pathologists reviewing slides) are not specified. Standard practice may involve independent review, but it's not detailed here.
- Viral Inactivation: Not applicable.
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:
- Not applicable. This device is a bone void filler, not an AI-powered diagnostic imaging device.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Not applicable. This is a physical medical device.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Osteoinductivity: Histopathology (microscopic examination of tissue samples for the presence of osteoblasts, chondroblasts, and woven bone).
- Viral Inactivation: Quantitative virology assays (measuring reduction in viral titers).
The sample size for the training set:
- Not applicable. This is not an AI/machine learning device requiring a training set in that sense. The "training" for the product refers to the development and manufacturing processes.
How the ground truth for the training set was established:
- Not applicable. As above, it is not an AI/ML device.

Summary

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K081950

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Medtronic Sofamor Danek PROGENIX® Plus 510(k) Summary June 2008

'JUL 1 8 2008

Medtronic Sofamor Danek USA l. Company: 1800 Pyramid Place Memphis, TN 38132 Telephone: (901) 396-3133 Fax: (901) 346-9738
- Ryan Massey Contact: Regulatory Affairs Specialist
PROGENIX® Plus ll. Proposed Proprietary Trade Name: Resorbable calcium salt bone Classification Name: void filler device NUN Product Code: Regulation No .: 872.3930

Product Description/Purpose of Application ��.

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The purpose of this Special 510(k): Device Modification application is to include a new formulation (PROGENIX® Plus) to the previously cleared PROGENIX® product line. The subject device, like the predicate device, contains human demineralized bone matrix (DBM) in a biocompatible carrier, however PROGENIX® Plus will also contain two different sized demineralized bone particles. The indications for PROGENIX® Plus will be identical to the previously cleared PROGENIX® product (K080462, SE 05/13/08).

IV. Indications

Ridge augmentation Filling of cystic defect Filling of extraction sites Filling of lesions of periodontal origin Craniofacial augmentation Filling of defects of endodontic origin Mandibular reconstruction Repair of traumatic defects of the alveolar ridge, excluding maxillary and mandibular fracture Filling of resection defects in benign bone tumors, benign cysts or other osseous defects in the alveolar ridge wall.

V. Substantial Equivalence

Documentation is provided that demonstrates PROGENIX® Plus is substantially equivalent to previously cleared bone void fillers such as PROGENIX® DBM

1081950

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Putty (Medtronic Sofamor Danek, K080462, SE 05/13/08) and GRAFTON® DBM Crunch (Osteotech Inc., K051188, SE 01/03/06).

Osteoinductivity Potential VI.

All DBM used in the preparation of PROGENIX® Plus must induce bone formation when evaluated in a validated athymic nude rat assay. Additionally, PROGENIX® must also induce bone formation in this assay system prior to being released for use. The raw material and final product screening must show histologic evidence of osteoinduction through the presence of osteoblasts, chrondoblasts and/or woven bone. Osteoinduction assay results using the athymic rat assay should not be interpreted to predict clinical performance in human subjects.

VIII. Viral Inactivation

PROGENIX® Plus is produced from tissue and collagen that undergoes processing steps validated to inactivate a panel of viruses representative of those that are clinically relevant. The cortical bone used to produce the DBM undergoes a proprietary process demonstrated to inactivate viruses. Furthermore, the DBM undergoes additional steps that are also effective at inactivating viruses. The viral inactivation testing demonstrates suitable viral inactivation potential of the processing methods for a wide range of potential human viruses. These processing steps further reduce the risk of viral contamination beyond donor screening and testing.

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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 consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. Ryan Massey Regulatory Affairs Specialist Medtronic Sofamor Danek USA 1800 Pyramid Place Memphis, Tennessee 38132

[JUL 1 8 2008

Re: K081950 Trade/Device Name: PROGENIX® Plus Regulation Number. 21CFR 872.3936 Regulation Name: Bone Grafting Material Regulatory Class: II Product Code: NUN Dated: July 3, 2008 Received: July 9, 2008

Dear Mr. Massey:

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. Massey

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.

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 Center for Devices and Radiological Health's (CDRH's) Office of Compliance at (240) 276-0115. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Suze Puns
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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K 081950

510(k) Number (if known):

PROGENIX® Plus Device Name:

Indications for Use:

Ridge augmentation

Filling of cystic defect

Filling of extraction sites

Filling of lesions of periodontal origin

Craniofacial augmentation

Filling of defects of endodontic origin

Mandibular reconstruction

Repair of traumatic defects of the alveolar ridge, excluding maxillary and mandibular fracture

Filling of resection defects in benign bone tumors, benign cysts or other osseous defects in the alveolar ridge wall.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Susan Rioner

(Division Sign-Off) (Division Sign-On)
Division of Anesthesiology, General Hospital Infection Control, Dental Devices

510(k) Number: _

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.