PROGENIX® Plus is intended for use as a bone graft substitute in bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure (i.e. spine, pelvis and extremities). The voids or gaps may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. PROGENIX® Plus provides a bone void filler that is resorbed/remodeled and is replaced by host bone during the healing process. The device may either be use alone or mixed with autograft bone and used as a bone graft extender.

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 versions: Putty and Plus. PROGENIX® Plus is a putty containing two different sized demineralized bone particles. PROGENIX® is a single use product intended for use as a bone graft substitute. bone graft extender 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. Additionally, this product is not designed to impart any mechanical strength to the surgical site. PROGENIX® is provided in ready-to-use malleable forms that may be molded or manipulated by the surgeon into various shapes. This product has been shown to be osteoconductive as well as osteoinductive in an athymic rat assay, allowing for bony ingrowth across the graft site while resorbing at a rate consistent with bony healing.

AI/ML Overview

This is a 510(k) premarket notification for a medical device called PROGENIX® Plus, a bone void filler. This document is not a study report or clinical trial. It is a regulatory submission to the FDA to demonstrate substantial equivalence to a predicate device.

Therefore, the requested information about acceptance criteria, device performance tables, sample sizes, expert ground truth, adjudication methods, MRMC studies, standalone AI performance, and training set details are not applicable in this context.

Instead, the document focuses on demonstrating that PROGENIX® Plus is substantially equivalent to previously cleared devices based on its composition, intended use, and pre-clinical testing, primarily in an athymic rat assay for osteoinductivity and viral inactivation studies.

Here's a breakdown of what is available in the document related to some of your points:

1. A table of acceptance criteria and the reported device performance:

Acceptance Criteria (Implicit for Substantial Equivalence):
- Osteoinductivity: "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." (Page 2)
- Histologic evidence: "The raw material and final product screening must show histologic evidence of osteoinduction through the presence of osteoblasts, chrondoblasts and/or woven bone." (Page 2)
- Viral Inactivation: Processing steps must be "validated to inactivate a panel of viruses representative of those that are clinically relevant." (Page 2)
- Intended Use, Technology, Performance: Demonstrate equivalence to predicate devices (PROGENIX® DBM Putty and GRAFTON® DBM Crunch) in terms of intended use, technological characteristics, and performance characteristics (as supported by pre-clinical data).
Reported Device Performance (as stated in the document):
- Osteoinductivity: "This product has been shown to be osteoconductive as well as osteoinductive in an athymic rat assay, allowing for bony ingrowth across the graft site while resorbing at a rate consistent with bony healing." (Page 1) and "Osteoinduction assay results using the athymic rat assay should not be interpreted to predict clinical performance in human subjects." (Page 2)
- Viral Inactivation: "The viral inactivation testing demonstrates suitable viral inactivation potential of the processing methods for a wide range of potential human viruses." (Page 2)

2. Sample sized used for the test set and the data provenance:

Not applicable for clinical studies. This document refers to an "athymic nude rat assay" for osteoinductivity. The sample size for this assay is not provided, nor is the provenance of data as it's a pre-clinical, lab-based assay.

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

Not applicable. This relates to clinical studies with expert reviewers, which is not the nature of this document.

4. Adjudication method for the test set:

Not applicable. This relates to clinical studies with expert reviewers, which is not the nature of this document.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done:

No, an MRMC comparative effectiveness study was not done. This is a regulatory submission based on substantial equivalence, not a clinical effectiveness trial in human subjects. The document explicitly states: "Osteoinduction assay results using the athymic rat assay should not be interpreted to predict clinical performance in human subjects." (Page 2)

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

Not applicable. This is not an AI/algorithm-based device. It is a biological product (bone graft substitute).

7. The type of ground truth used:

Pre-clinical animal model (athymic rat assay) for osteoinduction: Histologic evidence (presence of osteoblasts, chondroblasts, and/or woven bone) was used to assess osteoinductivity.
Laboratory-validated viral inactivation studies for viral safety.

8. The sample size for the training set:

Not applicable. This refers to AI/machine learning models, which is not relevant to this device.

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

Not applicable. This refers to AI/machine learning models.

In summary: The provided document is a 510(k) summary demonstrating substantial equivalence for a bone graft substitute, relying on pre-clinical animal and lab testing to support claims of osteoinductivity and viral inactivation. It does not involve clinical studies with human subjects, AI models, or the associated methodologies for evaluating such technologies.

Summary

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K082002

NOV 2 4 2008

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

1. Company: Medtronic Sofamor Danek USA 1800 Pyramid Place Memphis, TN 38132 Telephone: (901) 396-3133 Fax: (901) 346-9738
- Contact: Michelle Obenauer Regulatory Affairs Manager

II. Proposed Proprietary Trade Name:	PROGENIX® Plus
Classification Name:	Resorbable calcium salt bone void filler device
Product Code:	MQV and MBP
Regulation No.:	888.3045

lll. Product Description/Purpose of Application

PROGENIX® is a single use product intended for use as a bone graft substitute. bone graft extender 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. Additionally, this product is not designed to impart any mechanical strength to the surgical site. PROGENIX® is provided in ready-to-use malleable forms that may be molded or manipulated by the surgeon into various shapes. This product has been shown to be osteoconductive as well as osteoinductive in an athymic rat assay, allowing for bony ingrowth across the graft site while resorbing at a rate consistent with bony healing.

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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 contains two different sized demineralized bone particles as well as a change in the amount of sodium alginate. The indications for PROGENIX® Plus will be identical to the previously cleared PROGENIX® product (K072265, SE 01/09/08).

IV. Indications

Substantial Equivalence V.

Documentation is provided that demonstrates PROGENIX® Plus is substantially equivalent to previously cleared bone void fillers such as PROGENIX® DBM Putty (Medtronic Sofamor Danek, K072265, SE 01/09/08)and GRAFTON® DBM Crunch (Osteotech, Inc., K051195, SE 12/16/05),

VI. Osteoinductivity Potential

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

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1082002

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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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States of America. The seal features a stylized eagle with its wings spread, symbolizing protection and service. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle, indicating the department's name and national affiliation. The seal is presented in black and white.

Public Health Service

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

NOV 2 4 2008

Medtronic Sofamor Danek USA, Inc. % Ms. Michelle Obenauer Regulatory Affairs Manager 1800 Pyramid Place Memphis, Tennessee 38132

Re: K082002

Trade/Device Name: PROGENIX® Plus Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: II Product Code: MQV, MBP Dated: November 8, 2008 Received: November 10, 2008

Dear Ms. Obenauer:

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 indicons for use stated in the enclosure) to legally marketed predicate devices marketed in intribute commerce prior to May 28, 1976, the enactment date of the Medical Device Amendmounts 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 I.c. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbrandi, nomn 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 aftecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, TDA move 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 ecotonic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1000.

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Page 2 -- Ms. Michelle Obenauer

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 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) 276-0120. 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 Assistances at toll-free number (800) 638-2041 or (240) 276-3150 or Internet School http://www.fda.gov/cdrh/industry/support/index.html,

Sincerely yours.

Mark M. Millman

Mark N. Melkerson Director Division of General; Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure

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510(k) Number (if known):

Device Name: PROGENIX® Plus

Indications

Prescription Use _____________________________________________________________________________________________________________________________________________________________ AND/OR Over-The-Counter Use (Part 21 CFR 801 Subpart D) (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)

Mark N. Milhem

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

510(k) Number K082002

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.