filling of extraction sockets to enhance preservation of the alveolar ridge in contained situations with entirely intact, circumferential bone walls.
filling of contained periodontal defects of limited size with intact lingual and buccal walls, i.e. 3-wall intrabony defects.
filling of contained peri-implant defects of limited size to include 3-wall defects of a size up to 4 mm x 5 mm x 4 mm.

Device Description

Geistlich Bio-Flow® is a flowable, sterile, biocompatible bone mineral plus collagen matrix consisting of Geistlich Bio-Oss® granules (K122894) and processed Geistlich Bio-Gide® collagen (K212463) in an 80:20 (dry weight) ratio. Geistlich Bio-Flow® is provided as dry granulated material pre-filled in a mixing syringe (0.2 cc or 0.5 cc fill volumes). Cannulas and a syringe for applying saline or blood to hydrate the product prior to extrusion are included with the product.

AI/ML Overview

The provided text is a 510(k) Summary for a medical device (Geistlich Bio-Flow®), which focuses on demonstrating substantial equivalence to a predicate device rather than presenting a traditional clinical study with defined acceptance criteria and performance metrics for a diagnostic or AI-based device. This document describes the device, its intended use, and non-clinical performance data to support its safety and effectiveness. It does not contain an "acceptance criteria" table with specific thresholds or a detailed study of an AI device's performance against ground truth as would be found in a typical AI/diagnostic device submission.

However, I can extract the relevant information from the document that best approximates the requested points based on the nature of this submission. Since this is a bone grafting material, the "performance" is assessed through non-clinical (material characterization and animal) studies rather than a multi-reader, multi-case study, or standalone AI performance.

Here's an interpretation based on the provided text:

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

The document doesn't explicitly state quantitative acceptance criteria or a performance table in the format typically used for AI/diagnostic devices (e.g., sensitivity, specificity thresholds). Instead, "performance" is demonstrated through various non-clinical tests and a non-clinical animal study, with the overarching "acceptance criterion" being comparable performance to the predicate device in relevant biological and material characteristics.

Acceptance Criteria (Implied from the study's aim)	Reported Device Performance
Biocompatibility: Device demonstrates biological safety.	Positive: Biocompatibility Studies per ISO 10993-1:2018 (Cytotoxicity, Sensitization, Irritation/Intracutaneous Reactivity, Acute Systemic Toxicity, Material Mediated Pyrogenicity, Subacute Systemic Toxicity, Subchronic Systemic Toxicity, Chronic Systemic Toxicity, Implantation (local tissue reaction), Genotoxicity, Hemocompatibility) all performed and found acceptable (implied by clearance).
Physical and Chemical Properties: Material characteristics are suitable for intended use.	Positive: Characterization of chemical properties (Chemical composition, Amino Acid Composition, Molecular Weight Distribution of Soluble Proteins, Enzymatic Collagen Degradation, Collagen Solubility) and physical properties (Porosity and morphology, Particle (Granule) Size, Volume Changes after Incubation) were performed. Characterization of Mineral Component (Bovine Bone Mineral) via FTIR spectroscopy and X-ray diffraction was performed. Outcomes are not explicitly detailed but are presumed acceptable for substantial equivalence. Handling and extrusion studies (Extrusion Force, Material Handling with Blood, Extrudable Volume, Organic and Inorganic Content of Extruded Material) were also performed successfully.
Sterilization and Packaging: Device maintains sterility and integrity.	Positive: Sterilization Validation per ISO 11137-1:2006, ISO 11137-2:2013, and ISO 11137-3:2017. Packaging Validation per ISO 11607-1:2019, ASTM F1980:2007, ASTM F1886/F1886M:2016, ASTM F88:2015, ASTM F1929:2015, and ASTM F2096:2011.
Stability: Device remains stable over shelf life.	Positive: Product stability testing per ICH Q1A(R2) and Collagen stability studies (Molecular Weight Distribution of Soluble Protein 18-months storage, Enzymatic Collagen Degradation 18-months storage, Collagen Solubility 18-months storage) were performed.
Biological Performance (Animal Study): Device promotes bone regeneration and exhibits comparable resorption to predicate.	Positive: In a non-clinical animal performance study, no signs of adverse local tissue effects were observed with Geistlich Bio-Flow® at any time-point. At both 8 and 12 weeks, the bone substitute performance of the test and control groups (Geistlich Bio-Flow® vs. Geistlich Bio-Oss® Collagen) was comparable with respect to relevant parameters, such as Defect Fill Area, Bone Regeneration Height, and Bone-to-Granule-Contact.

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

Test Set (Animal Study): The document states "a non-clinical performance study was conducted to support the indications for use for the device," and "In a study assessing new bone growth and device resorption (4, 8, and 12 weeks), at both 8 and 12 weeks, the bone substitute performance of the test and control groups was comparable."
- Sample Size: The document does not specify the exact number of animals or defects studied.
- Data Provenance: Non-clinical (animal study). No country of origin is specified. It is a prospective study as it involved conducting tests with the device.

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

This information is not applicable to this type of submission. The performance study was an animal model, not a human reader study requiring expert interpretation to establish ground truth for a diagnostic output.

4. Adjudication method for the test set

This is not applicable as it was not a human reader study. The animal study results would likely be evaluated by veterinary histopathologists or researchers in a blinded manner, but no specific adjudication method (like 2+1) is mentioned.

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, an MRMC comparative effectiveness study was not done. This device is a bone grafting material, not a diagnostic or AI-assisted device.

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

No, a standalone performance study in the context of an algorithm or AI was not done.

7. The type of ground truth used

For the non-clinical performance study (animal study), the "ground truth" would be established by histological analysis (e.g., measurements of new bone formation, defect fill, and resorption characteristics) and potentially other quantitative analyses in the animal model. This falls under outcomes data simulation in an animal model.

8. The sample size for the training set

This concept (training set) is not applicable to the evaluation of this bone grafting material. There is no AI model being trained.

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

This concept is not applicable as there is no AI model or training set.

Summary

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

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Geistlich Pharma AG % Roshana Ahmed Sr. Regulatory Specialist TELOS Partners LLC 2850 Frontier Drive Warsaw, Indiana 46582

March 07, 2025

Re: K242510

Trade/Device Name: Geistlich Bio-Flow® Regulation Number: 21 CFR 872.3930 Regulation Name: Bone Grafting Material Regulatory Class: Class II Product Code: NPM Dated: January 31, 2025 Received: January 31, 2025

Dear Roshana Ahmed:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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.

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

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatory

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

assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Sherrill Lathrop Blitzer

Andrew Steen for Assistant Director DHT1B: Division of Dental and ENT Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT, and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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

Indications for Use

510(k) Number (if known) K242510

Device Name Geistlich Bio-Flow(R)

Indications for Use (Describe)

Geistlich Bio-Flow® is intended for bone regeneration of contained defects around teeth or dental implants for the following uses:

filling of extraction sockets to enhance preservation of the alveolar ridge in contained situations with entirely intact, circumferential bone walls.
filling of contained periodontal defects of limited size with intact lingual and buccal walls, i.e. 3-wall intrabony defects.
filling of contained peri-implant defects of limited size to include 3-wall defects of a size up to 4 mm x 5 mm.

Type of Use (Select one or both, as applicable)
Research Use (Part 21 CFR 361. Subpart B)	Over-the-Counter Use (21 CFR 361 Subpart C)

Prescription Use (Part 21 CFR 801 Subpart D)

__ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

510(k) Summary

I. Submitter

Geistlich Pharma AG Bahnhofstrasse 40 CH-6110 Wolhusen Switzerland Phone: +41 41 492 55 55

Contact Person: Marco Steiner, Deputy Director Regulatory Affairs Date Prepared: March 7, 2025

II. Device

Device Proprietary Name:	Geistlich Bio-Flow®
Common or Usual Name:	Bone Grafting Material
Classification Name:	Bone grafting material, animal source
Regulation Number:	872.3930
Product Code:	NPM
Device Classification:	II

III. Predicate Device

Substantial equivalence is claimed to the following device:

Product Name	510(k)	Applicant
Geistlich Bio-Oss® Collagen	K122894	Geistlich Pharma AG

Reference devices:

. Geistlich Bio-Oss®, K240661, Geistlich Pharma AG
Geistlich Bio-Gide®, K212463, Geistlich Pharma AG .
. Geistlich Bio-Oss Pen, K120601, Geistlich Pharma AG
. Novabone, K091484, NovaBone Products, LLC

IV. Device Description

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

syringe for applying saline or blood to hydrate the product prior to extrusion are included with the product.

V. Indications for Use

Geistlich Bio-Flow® is intended for bone regeneration of contained defects around teeth or dental implants for the following uses:

1. filling of extraction sockets to enhance preservation of the alveolar ridge in contained situations with entirely intact, circumferential bone walls.
1. filling of contained periodontal defects of limited size with intact lingual and buccal walls, i.e. 3-wall intrabony defects.
1. filling of contained peri-implant defects of limited size to include 3-wall defects of a size up to 4 mm x 5 mm x 4 mm.

VI. Comparison of Technological Characteristics

Geistlich Bio-Flow® is substantially equivalent to Geistlich Bio-Oss® Collagen in terms of intended use and technological characteristics. The table below provides a comparison of the intended use and key features for each product.

	Geistlich Bio-Flow®Subject Device	Geistlich Bio-Oss® Collagen(K122894)	Analysis
Manufacturer	Geistlich Pharma AG	Geistlich Pharma AG	Same
Indications forUse	Geistlich Bio-Flow® is intendedfor bone regeneration ofcontained defects around teeth ordental implants for the followinguses:1. filling of extraction socketsto enhance preservation ofthe alveolar ridge incontained situations withentirely intact,circumferential bone walls.2. filling of containedperiodontal defects oflimited size with intactlingual and buccal walls,	Geistlich Bio-Oss Collagen® isintended for the following uses:augmentation orreconstructive treatmentof the alveolar ridge filling of periodontaldefects filling of defects afterroot resection,apicoectomy, andcystectomy filling of extractionsockets to enhancepreservation of thealveolar ridge elevation of the maxillarysinus floor	SimilarTheindicationsfor usestatementforGeistlichBio-Flow®is a subsetof theclearedindicationsof thepredicatedevice.Thisdifferencedoes notalter the

{6}------------------------------------------------

	Geistlich Bio-Flow®Subject Device	Geistlich Bio-Oss® Collagen(K122894)	Analysis

	i.e. 3-wall intrabony defects.3. filling of contained peri-implant defects of limited size to include 3-wall defects of a size up to 4 mm x 5 mm x 4 mm.	filling of periodontal defects in conjunction with products intended for Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) filling of peri-implant defects in conjunction with products intended for Guided Bone Regeneration (GBR).	intended use of the subject device when compared to the intended use of the predicate device.
Materials ofConstruction(Implant)	Geistlich Bio-Oss® bone mineral (bovine) + Collagen (porcine)	Geistlich Bio-Oss® bone mineral (bovine) + Collagen (porcine)	Same
AnimalSourcedMaterial	Bovine bonePorcine collagen	Bovine bonePorcine collagen	Same
Form/ Shape	Dry granules provided in pre-filled syringe to be pre-wetted	Dry block to be pre-wetted	Similar
Particle Size	125 - 180 mm	250 – 1000 μm	Different
Single-Use	Yes	Yes	Same
Sterilization	X-ray	Gamma-ray	Similar

Geistlich Bio-Flow® and the predicate device are single-use, radiation-sterilized, dental bone grafting materials composed of bovine bone granules and porcine collagen. The slight differences between the subject and predicate devices with respect to the indications for use statement restrict the indications for use of the subject device to contained defects of specific type and limited size; however, these differences do not alter the overall intended use of the subject device when compared to the intended use of the predicate device.

Geistlich Bio-Flow® is a flowable paste-like biomaterial containing Geistlich Bio-Oss® hydroxyapatite granules sizes ranging from 125 -180 um, and processed Geistlich Bio-Gide® collagen. The Geistlich Bio-Flow® granules are derived from the same manufacturing process as the granules used for the predicate device. The subject and predicate device are considered substantially equivalent with respect to materials of construction as the main components for both products are bone mineral matrix and the collagen carrier.

{7}------------------------------------------------

Provided in a pre-filled syringe, Geistlich Bio-Flow® must be hydrated with saline or blood prior to application using an 17G cannula. A 1 mL syringe is provided with the product to allow for introduction of saline or blood into the pre-filled mixing syringe.

VII. Performance Data

The following non-clinical tests were performed to support substantial equivalence:

. Characterization of chemical properties
- Chemical composition 100 % by mass o
- Amino Acid Composition O
- Molecular Weight Distribution of Soluble Proteins о
- Enzymatic Collagen Degradation O
- Collagen Solubility о
Characterization of physical properties ●
- Porosity and morphology O
- Particle (Granule) Size O
- Volume Changes after Incubation o
Additional studies ●
- Collagen stability studies O
  - I Molecular Weight Distribution of Soluble Protein 18-months storage
  - Enzymatic Collagen Degradation 18-months storage
  - I Collagen Solubility 18-months storage
- Handling studies and extrusion studies O
  - Extrusion Force
  - l Material Handling with Blood
  - Extrudable Volume
  - I Organic and Inorganic Content of Extruded Material
- Characterization of Mineral Component (Bovine Bone Mineral) O
  - . FITR spectroscopy
  - 트 X-ray diffraction
Sterilization Validation per ISO 11137-1:2006, ISO 11137-2:2013, and ISO 11137-● 3:2017
Packaging Validation per ISO 11607-1:2019, ASTM F1980:2007, ASTM F1886/F1886M:2016, ASTM F88:2015, ASTM F1929:2015, and ASTM F2096:2011
Product stability testing per ICH Q1A(R2) ●
Biocompatibility Studies per ISO 10993-1:2018 ●
- Cytotoxicity per ISO 10993-5:2009 O
- Sensitization per ISO 10993-10:2021 O
- Irritation/Intracutaneous Reactivity per ISO 10993-10:2021 O
- Acute Systemic Toxicity per ISO 10993-11:2017 O

{8}------------------------------------------------

Material Mediated Pyrogenicity per USP <151> / Ph. Eur. Section 2.6.8 o
Subacute Systemic Toxicity per ISO 10993-6:2016 and ISO 10993-11:2017 O
Subchronic Systemic Toxicity per ISO 10993-6:2016 and ISO 10993-11:2017 о
Chronic Systemic Toxicity per ISO 10993-11:2017 о
Implantation (local tissue reaction) per ISO 10993-6:2016 о
O Genotoxicity per ISO 10993-3:2014
Hemocompatibility per ASTM F756:2017 and ISO 10993-4:2017 O

A non-clinical performance study was conducted to support the indications for use for the device. Under the conditions of the animal performance study, no signs of adverse local tissue effects were observed with Geistlich Bio-Flow® at any time-point. In a study assessing new bone growth and device resorption (4, 8, and 12 weeks), at both 8 and 12 weeks, the bone substitute performance of the test and control groups was comparable. Based on the findings of the animal performance study, the test article Geistlich Bio-Flow® and the predicate device Geistlich Bio-Oss® Collagen shows comparable performance with respect to relevant parameters, such as Defect Fill Area, Bone Regeneration Height as well as Bone-to-Granule-Contact and therefore, substantial equivalence to the predicate Geistlich Bio-Oss® Collagen is established.

VIII. Conclusion

The information provided above supports that Geistlich Bio-Flow® is substantially equivalent to the predicate device. Although minor differences in design and technology exist between the subject and predicate device, performance testing demonstrates that these differences do not raise safety and effectiveness concerns.

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.