InterCollagen® Guide alone or in combination with suitable augmentation materials (like autogenous bone, allogeneic, xenogeneic or alloplastic bone replacement materials) is immediate or delayed guided tissue and bone regeneration.

· in the context of a treatment of fenestration defects
· in case of dehiscence defects
· after apicoectomy and resection of retained teeth
· in extraction sockets after tooth extractions
· in case of immediate or delayed augmentation around implants in extraction sockets

Device Description

InterCollagen® Guide is a resorbable collagen membrane, derived from porcine pericardium. InterCollagen® Guide is intended for periodontal and/or dental surgical procedures as a barrier membrane restricting the entry of rapidly proliferating non-osteogenic cells within the bone defect while allowing the ingrowth of slow-growing bone forming cells. The membrane is a bioresorbable barrier which eventually is remodeled and/or incorporated by the host tissue. InterCollagen® Guide is substantially resorbed within 15 weeks after implantation. It is adaptable and easy to handle. It can be trimmed to the desired size and conforms easily when hydrated. The product is terminally sterilized via gamma irradiation.

AI/ML Overview

This FDA 510(k) summary describes the InterCollagen® Guide, a resorbable collagen membrane. The submission seeks to prove substantial equivalence to a predicate device, the Straumann Jason Membrane, rather than demonstrate strict acceptance criteria and performance against those criteria. Therefore, the response will be structured to extract relevant performance claims and the study details provided, even if they don't explicitly fit a "table of acceptance criteria" format with numerical targets.

1. Table of Acceptance Criteria and Reported Device Performance

As this is a 510(k) submission seeking substantial equivalence, explicit numerical "acceptance criteria" with defined thresholds are not typically presented in the same way as a de novo or PMA submission. Instead, the focus is on demonstrating similar performance to a legally marketed predicate device. The following table summarizes the key performance aspects that were evaluated and the results presented, which essentially serve as the "reported device performance" against the implicitly accepted standard of the predicate device's performance.

Performance Aspect	Acceptance Standard (Implicitly based on Predicate Device)	Reported Device Performance (InterCollagen® Guide)
Biocompatibility	Meets ISO 10993 requirements for medical devices.	Non-mutagenic (Mouse Lymphoma, Ames Test)
(General)		Non-sensitizer (Kligman Maximization)
		Non-irritant (Intracutaneous irritation)
		Non-cytotoxic (Cytotoxicity L929 Neutral Red uptake)
		Non-toxic (Acute Systemic Toxicity, 90-day Subchronic Toxicity)
		Non-pyrogenic (Pyrogenicity)
		Minimum tissue reaction at 2, 11, and 15 weeks of implantation; no adverse tissue reaction to the host (Local effects after Implantation)
In Vivo Performance	Performance substantially equivalent to the predicate device (Jason membrane) in a canine model, with similar histological, histomorphometric, and micro-CT outcomes.	Performed in a manner substantially equivalent to the cleared predicate device across pathology, histology, histomorphology, and micro-CT endpoints.
Resorption Time	Substantially resorbed by 12 weeks (Predicate device: Straumann Jason Membrane)	Substantially resorbed by 15 weeks
Sterility Assurance	Sterility Assurance Level (SAL) of 10^-6 (Predicate device also achieves this)	Achieves a Sterility Assurance Level of 10^-6 (via Irradiation)
Viral Inactivation	Meets ISO 22442-3	Viral inactivation studies performed in accordance with ISO 22442-3 to ensure viral safety.
Pyrogenicity (Batch)	Non-pyrogenic (release test)	Each batch tested for endotoxin (LAL test, USP <85>, USP <161>) as finished product release test.
Shelf Life/Stability	Performance testing of packaging system; Selection, qualification, and validation of packaging.	Product and packaging stability determined using real-time aging data; Packaging tested per ASTM D4169, ISO 11607.

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

The primary "test set" for performance evaluation was the canine two-wall intrabony defect model.

Sample Size: Not explicitly stated in terms of the number of animals or defects. The document mentions "End points for pathology, histology, histomorphology and micro-CT were taken after 2, 6, and 13 weeks," implying a longitudinal study.
Data Provenance: Conducted as an animal study (canine model). The country of origin is not specified in the provided text. The study design was a comparison between the test article (InterCollagen® Guide), a predicate device (Jason membrane), and an empty control. This is a prospective study design for evaluating the device's performance post-implantation.

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

The document does not explicitly state the number or qualifications of experts used to establish ground truth for the animal study. Histology, histomorphology, and pathology evaluations are typically conducted by trained veterinary pathologists or researchers specialized in bone regeneration, but specific details are not provided.

4. Adjudication method for the test set

The document does not specify any adjudication method for establishing ground truth in the animal study. Evaluations of pathology, histology, histomorphology, and micro-CT are usually performed by experts, but whether independent reviews or consensus methods were used is not 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

A multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is a resorbable collagen membrane for guided bone and tissue regeneration, not an AI-assisted diagnostic or interpretative tool. Therefore, the concept of "human readers improve with AI" is not applicable here.

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

A standalone performance study of an algorithm was not performed. This is a medical device (collagen membrane), not a software or AI/ML algorithm.

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

For the animal study:

Pathology: Evaluation of pathological changes in tissues.
Histology: Microscopic examination of tissue samples.
Histomorphology: Quantitative analysis of tissue morphology (e.g., bone formation).
Micro-CT: Three-dimensional imaging for bone volume and structure analysis.

These are considered objective biological and imaging endpoints, typically interpreted by experts, to establish the "ground truth" regarding the device's in-vivo performance and tissue response.

8. The sample size for the training set

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

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

This is not applicable as there is no training set for this type of medical device.

Summary

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08/17/23

SigmaGraft Inc. Elcin Chang General Manager 575 Sally Place Fullerton, California 92831

Re: K223912

Trade/Device Name: InterCollagen® Guide Regulation Number: 21 CFR 872.3930 Regulation Name: Bone Grafting Material Regulatory Class: Class II Product Code: NPL Dated: July 26, 2023 Received: July 26, 2023

Dear Elcin Chang:

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. 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 located 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.

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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 803) for devices or postmarketing safety reporting (21 CFR 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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-regulatoryassistance/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

for Andrew Steen 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

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Indications for Use

510(k) Number (if known) K223912

Device Name InterCollagen® Guide

Indications for Use (Describe)

· in the context of a treatment of fenestration defects
· in case of dehiscence defects
· after apicoectomy and resection of retained teeth
· in extraction sockets after tooth extractions
· in case of immediate or delayed augmentation around implants in extraction sockets

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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Date Prepared:

FDA 510(k) Summary

August 16, 2023

Submitter's Contact Information

Submitter:	SigmaGraft, Inc. 575 Sally Place Fullerton, CA 92831, USA
Contact Person:	Elcin Chang
Phone Number:	+1-714-525-0112
Fax Number:	+1-714-525-0116
Prepared By:	Elcin Chang, General Manager

Email:

Name of the Device

Trade Names: Common Name: Classification Name: Regulation Number: Device Classification: Product Code(s): Classification Panel:

Predicate Device

Primary Predicate: Common Name: Classification Name: Regulation Number: Device Classification: Product Code(s): Classification Panel:

InterCollagen® Guide Bone Grafting Material Barrier, Animal Source, Intraoral នូវ72.3930 II NPL Dental

e.chang@sigmagraft.com

Straumann Jason Membrane (K173562) Bone Grafting Material Barrier, Animal Source, Intraoral ន្ល872.3930 II NPL Dental

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Device Description

Sizes

Type	Size (mm)	Product code
Resorbable Collagen Membrane	12 x 25	ICG1225
	15 x 20	ICG1520
	20 x 30	ICG2030
	25 x 25	ICG2525
	30 x 40	ICG3040

InterCollagen® Guide is provided in five different sizes:

Indications for Use

InterCollagen® Guide alone or in combination with suitable augmentation materials (like autogenous bone, allogeneic, xenogeneic or alloplastic bone replacement materials) can be used in guided bone regeneration (GBR) and guided tissue regeneration (GTR) procedures as a biodegradable barrier for:

. in the context of a treatment of fenestration defects
in case of dehiscence defects
after apicoectomy and resection of retained teeth
in extraction sockets after tooth extractions
in case of immediate or delayed augmentation around implants in extraction sockets ●

Summary/Comparison of Technical Characteristics

The subject device has substantially equivalent technological characteristics to the marketed predicate device. A comparison of the relevant technological characteristics between the subject and primary predicate device is provided in the table that follows.

Biocompatibility Testing

A series of in vitro and in vivo biocompatibility testing was performed to assess the safety of the subject device. Testing was determined in accordance with ISO 10993-1 and FDA Guidance on

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Use of International Standard ISO 10993-1 for the biological evaluation of medical devices within a risk management process.

The biocompatibility testing performed is summarized in the table below.

Test	Standards	Result
Mouse Lymphoma forward mutationassay	ISO 10993-3,OECD 476, OECD490	Non-mutagenic
Genotoxicity (Ames: BacterialReverse Mutation) Test	ISO 10993-3	Non-mutagenic
Kligman Maximization SensitizationTest	ISO 10993-10	Non-sensitizer
Intracutaneous irritation test	ISO 10993-10	Non-irritant
Cytotoxicity L929 Neutral Reduptake test	ISO 10993-5	Non-cytotoxic
Acute Systemic Toxicity Test	ISO 10993-11	Non-toxic
90 day Subchronic Toxicity Test	ISO 10993-11	Non-toxic
Pyrogenicity (material mediated)	ISO 10993-11	Non-pyrogenic
Local effects after Implantation Test	ISO 10993-6	Minimum tissue reaction at 2, 11,and 15 weeks of implantation andno adverse tissue reaction to thehost

Animal Testing

The performance of the device in a canine two-wall intrabony defect model was compared to the performance of the predicate device, Jason membrane. The objective of this study was to evaluate the in vivo performance, local effects following implantation, and systemic toxicity of the test article, InterCollagen® Guide, in comparison to a predicate and empty control.

End points for pathology, histology, histomorphology and micro-CT were taken after 2, 6, and 13 weeks. The subject device performed in a manner substantially equivalent to the cleared predicate device.

Animal Tissue Management

Animal tissues are managed in accordance with the following standards and guidance documents:

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ISO 22442-1 Animal Tissues and Their Derivatives Utilized in the Manufacture of Medical Devices - Part 1: Analysis and Risk Management
ISO 22442-2 Animal Tissues and Their Derivatives Utilized in the Manufacture of ● Medical Devices - Part 2: Controls on Sourcing, Collection, and Handling
ISO 22442-3 Animal Tissues and Their Derivatives Utilized in the Manufacture of ● Medical Devices – Part 3: Validation of the Elimination and/or Inactivation of Viruses and Transmissible Agents
Medical Devices Containing Materials Derived from Animal Sources (Except for In ● Vitro Diagnostic Devices) Guidance for Industry and Food and Drug Administration Staff, CDRH, FDA, March 15, 2019
FDA Guidance for Industry Q5A Viral Safety Evaluation of Biotechnology Products ● Derived from Cell Lines of Human or Animal Origin, CDER, CBER, September 1998

Sterilization

Sterilization validation was performed in accordance with ISO 11137-1 Sterilization of health care products – Radiation Part 1 Requirements for development, validation and routine control of a sterilization process for medical devices, ISO 11137-2 Sterilization of health care products – Radiation Part 2 Establishing the sterilization dose, and ISO 11737 Sterilization of Medical Devices – Microbiological Method – Determination of the Population of Microorganisms on Products.

Pyrogenicity

This device is non-pyrogenic. Each batch of product manufactured is tested for endotoxin per the Limulus Amebocyte Lysate (LAL) endotoxin test, USP <85> and USP <161>, as finished product release test.

Shelf Life and Stability

Product and packaging stability was determined using real-time aging data. Performance testing of packaging system was tested in accordance with ASTM D4169 Standard Practice for Performance Testing of Shipping Containers and Systems. Selection, qualification, and validation of packaging were conducted in accordance with ISO 11607 Packaging for Terminally Sterilized Medical Devices – Requirements for Materials, Sterile Barrier Systems, and Packaging Systems.

Viral Inactivation

Viral inactivation studies were performed in accordance with ISO 22442-3 to ensure the viral safety of the product.

Clinical Studies

Clinical performance data was not required to determine substantial equivalence.

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Conclusion

Chemical, physical, and biocompatibility tests as well as pre-clinical data show that the subject device is substantially equivalent to the predicate device. Comparison with the predicate device shows that the device has similar specifications and performance. Therefore, the conclusions drawn from the nonclinical and preclinical tests demonstrate that the device is substantially equivalent to its predicate device.

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Feature	InterCollagen® Guide(K223912)	Straumann Jason Membrane(K173562)	Equivalence Discussion
	Test article	Predicate device
Indicationsfor Use	InterCollagen® Guide alone or incombination with suitableaugmentation materials (likeautogenous bone, allogeneic,xenogeneic or alloplastic bonereplacement materials) can beused in guided bone regeneration(GBR) and guided tissueregeneration (GTR) procedures asa biodegradable barrier for:in the context of a treatmentof fenestration defects in case of dehiscence defectsafter apicoectomy andresection of retained teeth in extraction sockets aftertooth extractions in case of immediate ordelayed augmentation aroundimplants in extraction sockets	Jason membrane alone or incombination with suitableaugmentation materials (likeautogenous bone, allogeneic,xenogeneic or alloplastic bonereplacement materials) is indicatedfor immediate or delayed guidedtissue and bone regeneration.In case of surgical bone defectsand bone wall defects In the context of sinus flooraugmentation and support of theSchneiderian membrane In the context of Maxillary ridgeaugmentation In the context of Maxillary ridgereconstruction for prosthetic In the context of TreatmentFenestration defects In case of Periodontal bonedefects (1-3 wall defects) andfurcation defects (class I and II) In case of Dehiscence defects afterapicectomy, cystectomy, resectionof retained teeth and resection ofother bone lesions	EquivalentBoth devices are indicated forimmediate or delayed guidedtissue and bone regeneration.The indications for the subjectdevice are a subset of theindications for the predicatedevice.

		In extraction sockets after tooth extractions In case of immediate or delayed augmentation around implants in extraction sockets
Mode of Action	InterCollagen® Guide is a bio-resorbable barrier which eventually is remodeled and/or incorporated by the host tissue.	Jason Membrane is a bio-resorbable barrier which eventually is remodeled and/or incorporated by the host tissue.	EquivalentBoth devices are resorbable and function as a barrier to provide adequate new bone formation without soft tissue infiltration.
Operating Principle	Cell-occlusiveImplantableResorbableBiocompatible	Cell-occlusiveImplantableResorbableBiocompatible	EquivalentBoth devices function as a barrier to provide adequate new bone formation without soft tissue infiltration. They are both implantable, resorbable, and biocompatible.
Material origin	Porcine pericardium	Porcine pericardium	EquivalentBoth devices use a native collagen membrane obtained from porcine pericardium.
Collagen Type	Collagen Type I and Type III	Collagen Type I	EquivalentBoth devices have mainly Collagen Type I.
Form	Membrane	Membrane	Equivalent
			They act as a barrier against the infiltration of cells not involved in bone formation.
Color	White to off white	White to off white	EquivalentBoth devices have color that is white to off white.
Sizes	12 x 25 mm15 x 20 mm20 x 30 mm25 x 25 mm30 x 40 mm	15 x 20 mm20 x 30 mm30 x 40 mm	EquivalentBoth devices are provided in clinically relevant sizes for intra-oral surgical procedures.
ResorptionTime	Substantially resorbed by 15 weeks	Substantially resorbed by 12 weeks	EquivalentThe longer endurance of the desired barrier properties provides adequate new bone formation without soft tissue infiltration.
SterilizationMethod	Irradiation	Ethylene Oxide	EquivalentBoth the subject and predicate device achieve a Sterility Assurance Level of 10-6.
SingleUse/Reuse	Single use only	Single use only	EquivalentBoth devices are single use only.
Packaging	Double blister pack	Double pouch pack	EquivalentBoth devices facilitate aseptic delivery of the sterile device into the sterile surgical field

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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.