Coaptite™ Tissue Marker is a sterile, nonpyrogenic, flexible, semi-solid, cohesive implant used as a single use tissue marker. The principle component of the Coaptite™ Tissue Marker is synthetic calcium hydroxylapatite, a radiopaque biomaterial with over twenty years of use in orthopedics, neurosurgery, dentistry, otolaryngology, and ophthalmology. The product is available in two particle size ranges to allow different needle sizes for percutaneous placement. Coaptite™ Tissue Marker (0008025-1 and 0008026-1) has a size range of 75-125 microns. Coaptite™ FN Tissue Marker (0008027-1 and 0008028-1) has a size range of 25-45 microns. The calcium hydroxylapatite beads are clearly visible on standard radiographs as well as CT scan, MRI, and ultrasound. The cohesive semi-solid, elastic nature of the Coaptite™ Tissue Marker is created by physical bonds formed with sodium carboxymethylcellulose (NaCMC). NaCMC has also been used safely as a biomaterial for over twenty years. Coaptite™ Tissue Marker is placed into soft tissue during open, percutaneous, or endoscopic procedures to radiographically mark a surgical location. There is no ferrous material used in the formulation for Coaptite™ Tissue Marker and therefore it is MRI compatible.

AI/ML Overview

This 510(k) submission for the Coaptite™ Tissue Marker (K012955) does not include a study with acceptance criteria and reported device performance in the way a typical AI/ML device submission would. The document is for a physical implantable tissue marker, not an AI/ML software device.

Therefore, many of the requested categories in your prompt are not applicable to this submission. I will address the relevant sections of your prompt based on the provided text, and explicitly state when information is not available or not applicable for this type of medical device submission.

Here's a breakdown based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

This type of information (e.g., sensitivity, specificity, accuracy) is not applicable to this physical device submission. The acceptance criteria for the Coaptite™ Tissue Marker are inherent in its design, materials, and manufacturing processes, aiming for safety and effectiveness through biocompatibility, sterilization, and visible radiographic marking.

Acceptance Criteria Category (Derived from document intent)	Reported Device Performance (Summary)
Material Biocompatibility	Nonantigenic, nonirritant, nontoxic. No concerns for long-term safety issues based on 36-month data. Proven record of excellent biocompatibility for synthetic dense calcium hydroxylapatite (ASTM-1185). USP grade pharmaceutical excipients (glycerin, NaCMC) have extensive safe use.
Radiographic Visibility	Clearly visible on standard radiographs, CT scan, MRI, and ultrasound.
MRI Compatibility	MRI compatible (no ferrous material).
Sterilization Efficacy	Sterilized using steam, validated autoclave system with overkill methodology to 10⁻⁶ SAL.
Long-Term Safety (Clinical)	Subjects from a clinical study (Robert Mayer, M.D.) are more than five years out from implant placement with no long-term concerns.
Substantial Equivalence to Predicates	Determined substantially equivalent to Durasphere Tissue Marker (K001807), Gel Mark Biopsy Site Marker (K000060), and Auto Suture Site Marker staple (K983400) for radiographic soft tissue marking.

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

Sample Size (Pre-clinical): The document mentions "in vivo tests" for sensitization, tissue reaction, systemic reactions, and long-term safety issues, conducted under GLP guidelines. However, the exact sample size (number of animals or test subjects) for these in vivo tests is not specified.
Sample Size (Clinical): "Subjects from the clinical study by Robert Mayer, M.D." are mentioned, but the exact number of subjects is not provided.
Data Provenance: The preclinical tests were "in vitro and in vivo" based on Tripartite and Biocompatibility guidelines and ISO10993, using historically accepted test methods. These tests were conducted under GLP (Good Laboratory Practice) guidelines, suggesting a controlled experimental environment. The clinical study by Dr. Robert Mayer would inherently be prospective in nature for assessing long-term outcomes, but the original study design details are not in this 510(k) summary. The country of origin for these studies is not specified, though BioForm, Inc. is located in Wisconsin, USA.

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

This concept is not directly applicable to this physical device submission. "Ground truth" in the context of material biocompatibility and radiographic visibility is established through objective scientific testing (e.g., chemical analysis, imaging studies) and established medical understanding of materials, rather than expert consensus on diagnostic interpretations. The document refers to "pre-clinical and clinical experience" and Dr. Robert Mayer's clinical study, implying medical expertise in evaluating outcomes, but no specific number or qualification of "experts establishing ground truth for a test set" on device performance in the AI sense is provided.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable to this device type. Adjudication methods are typically used in clinical studies for diagnostic devices where subjective interpretation (e.g., by radiologists) needs to be reconciled to establish a consensus ground truth. For a physical tissue marker, its presence and visibility are objectively verifiable.

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

Not applicable. This is a physical tissue marker, not an AI or diagnostic imaging device that assists human readers.

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

Not applicable. This is a physical tissue marker.

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

The "ground truth" for the performance of the Coaptite™ Tissue Marker is based on:

Biomaterial Science and Standards: Compliance with ASTM-1185 for calcium hydroxylapatite, and established safe use records for excipients (USP grade glycerin and sodium carboxymethylcellulose).
Pre-clinical In Vivo Testing: Direct measurement and observation of tissue reactions (sensitization, irritation, toxicity) in animal models, and long-term safety assessments (36-month data).
Radiographic Visibility: Objective imaging (X-ray, CT, MRI, ultrasound) to confirm the marker's presence and clarity.
Clinical Outcomes Data: "Long-term concerns" from subjects in a clinical study (Robert Mayer, M.D.) are considered. This refers to the real-world performance and safety in human subjects over an extended period.

8. The sample size for the training set

Not applicable. This is a physical device, not an AI/ML algorithm that requires a "training set."

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

Not applicable. Refer to point 8.

Summary

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K012955

OCT 2 2 2001

510(k) Premarket Notification Submission Coaptite™ Tissue Marker

510(k) Summary of Safety and Effectiveness

Trade Name:	Coaptite™ Tissue Marker and Coaptite™ FN TissueMarker
Common Name:	Tissue Marker
Classification Name:	Implantable Tissue Marker
Official Contact:	Victor M. BowersDirector Market DevelopmentBioForm, Inc.4133 Courtney RoadFranksville, WI 53126Phone 262-835-9800Fax 262-835-9311

Date Prepared: 8-31-01

Intended Use

Coaptite™ Tissue Marker is indicated for use to radiographically mark soft tissue during a surgical procedure or for future surgical procedures.

Product Description

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Substantial Equivalence

The following are predicate devices that are substantially equivalent to Coaptite™ Tissue Marker.

K001807 Durasphere Tissue Marker Carbon Medical Technologies 1290 Hammond Road St. Paul, MN 55110

K000060 Gel Mark Biopsy Site Marker SenoRx, Inc. 13766 Alton Parkway, Suite 144 Irvine, CA 92618

K983400 Auto Suture Site Marker staple United States Surgical Corporation 150 Glover Avenue Norwalk, CT 06856

Coaptite™ Tissue Marker is substantially equivalent to the Durasphere Tissue Marker (K001807) manufactured by Carbon Medical Technologies, Inc., St. Paul, MN., Gel Mark Biopsy Site Marker (K000060) manufactured by SenoRx Inc., Irvine, CA., and Auto Suture Site Marker staple (K983400) manufactured by United States Surgical Corporation, Norwalk, CT. The Federal Food and Drug Administration, following review of the 510(K) pre-marketing notifications submitted by each company, approved for manufacture and sale all three of the predicate Class II devices. The 510(K) Number for each product is provided above. All of these devices have the same indication for use as radiographis soft tissue marker.

Biocompatibility Evaluations

Coaptite™ Tissue Marker is primarily formulated from synthetic dense calcium hydroxylapaptite meeting ASTM-1185, which has a proven record of excellent biocompatibility. The gel component of Coaptite™ Tissue Marker is an aqueous formulation of USP grade pharmaceutical grade excipients (glycerin and sodium carboxymethylcellulose). These excipients have extensive use in intramuscular injections such as Cortone®, Decadron®, Kenalog®, and Dalalone®. The battery of preclinical safety studies, dog implant studies, and clinical studies have shown that Coaptite™ Tissue Marker is biocompatible when injected into various submucosal or other tissues of animals. Subjects from the clinical study by Robert Mayer, M.D. are now more than five years out from implant placement with no long term concerns.

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Sterilization

Coaptite is sterilized using steam; processing is performed in-house using a validated autoclave system. Cycle parameters were validated using an overkill methodology to 10to SAL. Sterilization by the user is not required.

Pre-Clinical Tests Performed

In vitro and in vivo tests were based on Tripartite and Biocompatibility guidelines and International Organization for Standardization ISO10993, Biological Evaluation of Medical Devices, using historically accepted test methods of biomedical materials or United States Pharmacopoeia references. These studies were conducted under GLP guidelines.

In vivo tests were performed to address sensitization, tissue reaction during short-term implantation, systemic reactions and long term safety issues. Results identified Coaptite™ Tissue Marker as nonantigenic, a nonirritant, and nontoxic with no concerns for long term safety issues based on thirty-six month data.

Summary

In summary Coaptite™ Tissue Marker is substantialy equivalent to three predicate devices which all have the same indication for use. The components used in Coaptite™ Tissue Marker are biocompatible based on the history of their use in multiple medical devices as well as from pre-clinical and clincial experience. Coaptite™ Tissue Marker is equivalent in its application and is as safe as the predicate devices named above.

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Image /page/3/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three curved lines representing its wings. The eagle is enclosed in a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is written around the perimeter of the circle.

OCT 22 2001

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. Victor M. Bowers Director of Market Development BioForm, Inc. 4133 Courtney Road, #10 Franksville, Wisconsin 53126

Re: K012955

Trade/Device Name: Coaptite™ Tissue Marker and Coaptite™ FN Tissue Marker Regulation Number: 21 CFR 878.4300 Regulation Name: Implantable Clip Regulatory Class: Class II Product Codes: NEU, GDW Dated: August 31, 2001 Received: September 04, 2001

Dear Mr. Bowers:

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.

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Page 2 - Mr. Victor M. Bowers

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 and additionally 21 CFR Part 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4659. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained 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,

Sus-Well &

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

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510(k) Premarket Notification Submission Coaptite™ Tissue Marker

Kol2955 510(k) Number (if known):

Device Name: Coaptite™ Tissue Marker

Indications For Use:

Coaptite™ Tissue Marker is indicated for use to radiographically mark soft tissue during a surgical procedure or for future surgical procedures.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Sh
Division Sign Off

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

510(k) Number K012953

Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

Regulation Number and Section

§ 878.4300 Implantable clip.

(a)
Identification. An implantable clip is a clip-like device intended to connect internal tissues to aid healing. It is not absorbable.(b)
Classification. Class II.