CopiOs™ BVF, in combination with autologous bone marrow, is intended for use only for filling bone voids or gaps of the skeletal system (ie, extremities, pelvis, spine) that are not intrinsic to the stability of the bone structure. These voids may be a result of trauma or creation by surgeon. CopiOs™ BVF is intended to be gently packed into the void or gap and will resorb during the course of the healing process.

Device Description

CopiOs™ BVF is a synthetic bone graft material consisting of mineralized, lyophilized collagen that has been formed into three-dimensional pads of various sizes for surgical implantation. The CopiOs™ BVF product sponge consists of dehydrothermally (DHT) cross-linked bovine dermal collagen mixed with calcium phosphate salt. The pads are approximately 67% mineral by weight. The fibrous collagen mixed with the calcium phosphate salt is cast into sponges as described in this application. The average porosity of the product was determined to be 93.39%, which allows for favorable conditions for cell migration and adherence to the collagenous matrix. Further, the calcium phosphate provides the mineral required for osteogenesis and the specific CopiOs™ BVF formulation provides a pH environment conducive for osteoinduction.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the CopiOs™ Bone Void Filler (BVF). The study supporting its substantial equivalence is a comparative animal study.

Here's an analysis of the acceptance criteria and study information, based on the provided document:

1. Table of acceptance criteria and the reported device performance

The document does not explicitly state quantitative "acceptance criteria" in the form of specific thresholds for success. Instead, it frames the performance in terms of "substantial equivalence" to a predicate device (HEALOS). The performance claims are qualitative comparisons.

Acceptance Criteria (Implied)	Reported Device Performance
Composition: Similar collagen and calcium phosphate components.	CopiOs™ BVF: 33% type 1 bovine collagen, 67% calcium phosphate salt. HEALOS (predicate): 70% collagen, 30% non-ceramic hydroxyapatite. (Note: While different percentages, the document asserts substantial equivalence.)
Physical Structure: Similar physical form and porosity.	CopiOs™ BVF: Mineralized, lyophilized collagen into 3D pads. Average porosity 93.39%. HEALOS (predicate): Supplied as lyophilized product. (Implied similar physical structure).
Resorption Rate: Resorbed by the body at a comparable rate.	CopiOs™ BVF & HEALOS: Resorption rates are "similar as evidenced in the comparative rabbit radial defect study."
Bone Regeneration/Remodeling: Promotes new bone formation and is remodeled equivalently.	CopiOs™ BVF & HEALOS: Both promote bone regeneration and are remodeled into new bone at equivalent rates "as demonstrated in the comparative rabbit radial defect study."
Intended Use & Target Population: Same use case and patient group.	CopiOs™ BVF & HEALOS: Intended for the same use (filling bone voids/gaps in skeletal system, combination with autologous bone marrow) and target populations.
Sterility: Device must be sterile.	CopiOs™ BVF & HEALOS: Both are sterile.
Favorable Environment for Cell Migration/Adherence: Provides suitable environment for cellular activity.	CopiOs™ BVF & HEALOS: Both provide a favorable environment for cell migration and adherence to the collagenous matrix.
pH Environment for Osteoinduction: Conducive to bone formation.	CopiOs™ BVF: Specific formulation provides a pH environment conducive for osteoinduction. (Not explicitly stated for HEALOS but implied through general equivalence).

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

Test Set Sample Size: The document mentions a "comparative rabbit radial defect study." The exact number of rabbits or defect sites used in this study (the "test set" for performance evaluation) is not specified in the provided text.
Data Provenance: The study was a "comparative rabbit radial defect study," indicating animal data. The country of origin is not explicitly stated, but the sponsor is based in Minneapolis, Minnesota. The study would be considered prospective in nature, as it's an experimental design to evaluate the device.

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

The document does not provide information on the number or qualifications of experts involved in establishing the ground truth for the rabbit study. Histological analysis or imaging interpretation, which would likely involve experts, is implied for assessing bone regeneration and resorption, but details are absent.

4. Adjudication method for the test set

The document does not specify an adjudication method for the test set.

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted, nor is this device an AI-based system. This question is not applicable to the provided information.

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

This question is not applicable as the device is a medical implant (bone void filler), not an algorithm or AI system.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

For the "comparative rabbit radial defect study," the ground truth for evaluating bone regeneration and resorption would likely be based on histopathology (microscopic examination of tissue samples) and potentially imaging analysis (e.g., radiography, micro-CT) of the radial defects. This would constitute a form of objective, scientific assessment.

8. The sample size for the training set

This device is not an AI/ML algorithm that requires a "training set" in the computational sense. Therefore, the concept of a training set sample size is not applicable. The "training" for this device's development would involve biological research and materials science, not data training.

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

As in point 8, the concept of a "training set" and its ground truth in the context of AI/ML is not applicable to this bone void filler device.

Summary

{0}------------------------------------------------

Centerpulse Spine-Tech, Inc.

K033679

510(K) SUMMARY 7.0

Name of 510(k) Sponsor:	Centerpulse Spine-Tech, Inc.
Sponsor Address:	7375 Bush Lake RoadMinneapolis, Minnesota 55439Telephone Number: (952) 830-6284Fax Number: (952) 832-5620
Sponsor Contact:	Tim MillerDirector Clinical and Regulatory Affairs
Proprietary Name of Device:	CopiOs™ Bone Void Filler (BVF)
Generic/Classification Name:	Resorbable Calcium Salt Bone Void Filler
Classification Number:	Class II
Product Code:	89MQV
Legally Marketed
Predicate Devices:	HEALOS Bone Graft Material (K012751);
	Collagraft Strip Bone Graft Matrix (K00122);
	Vitoss Scaffold SyntheticCancellous Bone Void Filler (K994337);
	Pro Osteon Implant 500RResorbable Bone Graft Filler/Bone Graft Material; 200R
	Resorbable Bone Graft Material (K980817, K990131,K0000515);
	Bio-Oss Collagen (K974399)

Device Description:

CopiOs™ BVF is a synthetic bone graft material consisting of mineralized, lyophilized collagen that has been formed into three-dimensional pads of various sizes for surgical implantation.

Page 20 of 22

1/3

{1}------------------------------------------------

The CopiOs™ BVF product sponge consists of dehydrothermally (DHT) cross-linked bovine dermal collagen mixed with calcium phosphate salt. The pads are approximately 67% mineral by weight. The fibrous collagen mixed with the calcium phosphate salt is cast into sponges as described in this application. The average porosity of the product was determined to be 93.39%, which allows for favorable conditions for cell migration and adherence to the collagenous matrix. Further, the calcium phosphate provides the mineral required for osteogenesis and the specific CopiOs™ BVF formulation provides a pH environment conducive for osteoinduction.

Intended Use:

Technological Characteristics:

The intended use, composition, physical structure, and target population of CopiOs™ BVF are substantially equivalent to the FDA cleared and legally marketed predicate device, HEALOS.

CopiOsTM BVF and the predicate device HEALOS are intended for the . same use and target populations.
CopiOs™ BVF and the predicate device HEALOS are sterile and provide . a favorable environment for cell migration and adherence to the collagenous matrix.
Both CopiOs™ BVF and the predicate device HEALOS are supplied as . lyophilized products.
Like HEALOS, the predicate device, CopiOs™ BVF contains . approximately 33% type 1 bovine collagen while HEALOS contains 70%. Additionally. CopiOs™ BVF contains 67% calcium phosphate salt while HEALOS contains approximately 30% non-ceramic hydroxyappatite.
CopiOs™ BVF and the predicate device HEALOS are resorbed following . surgical implantation. The resorption rate between CopiOsTM BVF and HEALOS are similar as evidenced in the comparative rabbit radial defect study.

Page 21 of 22

2/3

{2}------------------------------------------------

CopiOs™ BVF and the predicate device HEALOS both promote bone . regeneration and are remodeled into new bone at equivalent rates as demonstrated in the comparative rabbit radial defect study.

Conclusions:

The results from the tests conducted as described in this submission support the substantial equivalence of CopiOs™ BVF to the predicate device.

{3}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

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 a stylized image of an eagle with its wings spread.

Public Health Service

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

JUL - 7 2004

Ms. Kimberly Tokach Senior Regulatory Affairs Specialist Zimmer Spine 7375 Bush Lake Road Minneapolis, Minnesota 55439

Re: K033679

Trade Name: CopiOs™ Bone Void Filler Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler Regulatory Class: II Product Code: MQV Dated: April 28, 2004 Received: May 4, 2004

Dear Ms. Tokach:

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.

{4}------------------------------------------------

Page 2 – Ms. Kimberly Tokach

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 n you attire of Compliance at (301) 594-4659. 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/dsma/dsmamain.html

Sincerely yours,

Miriam C. Provost

Celia M. Witten, Ph.D., M.D. Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{5}------------------------------------------------

Indications for Use

510(k) Number (if known): K033679

Device Name: CopiOs™ BVF

Indications for Use:

CopiOs™ BVF, in combination with autologous bone marrow, is intended for use only for filling OplOS - BVT, in oornismation system (i.e., extremities, pelvis, spine) that are not intrinsic to bone volute of the bone structure. These voids may be a result of trauma or creation by the stablity of the bene care cantly packed into the void or gap and will resorb during the course of the healing process.

Prescription Use (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 OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Miriam C. Provost

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

Page 1 of 1

510(k) Number K093677

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.