Silk Voice® is indicated for vocal fold medialization and vocal fold insufficiency that may be improved by injection of a soft tissue bulking agent. Silk Voice® injection augments the size of the displaced or deformed vocal fold so that it may meet the opposing fold at the midline for improved phonation. Vocal fold insufficiency associated with serious aspiration difficulties may be an urgent indication.

Device Description

Silk Voice® is a sterile, non-pyrogenic, cohesive implant provided in a prefilled syringe and is a ready to use product. Silk Voice is comprised of porous bioabsorbable silk particles suspended in an isotonic, aqueous formulation of cross-linked, high molecular weight hyaluronic acid (HA). The crosslinked HA gel acts as a carrier for the silk particles to facilitate delivery. The main component of Silk Voice is silk particles, manufactured exclusively from regenerated silk fibroin protein, isolated from purified, silk fibers. When injected, Silk Voice provides immediate volume augmentation to the vocal fold tissue. The porous particles remain at the site of implantation, providing a scaffold for local tissue infiltration. This cellular infiltrated silk scaffold provides the long term restoration and augmentation.

Silk Voice prefilled syringes are provided in a kit with a catheter, that is designed for endoscopic delivery to the vocal fold. The catheter accessory provided in the kit is specifically designed for delivery of injectable materials into tissue during endoscopic procedures.

AI/ML Overview

Based on the provided text, the device in question is Silk Voice®, a vocal fold medialization system. The document is a 510(k) premarket notification of intent to market, and as such, it focuses on demonstrating substantial equivalence to a previously cleared predicate device, rather than proving that the device meets specific performance acceptance criteria in an independent clinical study that would be typical for an AI/ML device.

Therefore, many of the requested items (e.g., sample size for test set, number of experts for ground truth, MRMC study, standalone performance for an algorithm) are not applicable to this type of medical device clearance or the information provided. The "acceptance criteria" here are primarily around demonstrating substantial equivalence through non-clinical testing and comparison to the predicate.

Here's a breakdown of the available information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly numerical thresholds like sensitivity/specificity for an AI algorithm. Instead, they are based on demonstrating that the device's characteristics and performance are comparable to the predicate device, and that it meets established safety standards.

Acceptance Criterion (Based on Substantial Equivalence & Safety)	Reported Device Performance (for Silk Voice®)	Comparison to Predicate (Radiesse Laryngeal Implant K070090)
Intended Use: Vocal fold augmentation	Vocal fold augmentation	Same
Indication for Use: Vocal fold medialization and insufficiency improved by soft tissue bulking agent; augments vocal fold size for improved phonation; urgent indication for serious aspiration difficulties.	Matches predicate's indications.	Same
Intended User: ENT Specialists	ENT Specialists	Same
Composition: Particle component in aqueous gel carrier	Silk particles suspended in cross-linked HA; 30-40% particle by volume	Similar (Predicate: CaHA particles in CMC; 30-40% by volume) - Functionally equivalent.
Particle component dimensions: (for comparison to predicate)	380 ± 46 um in diameter; 30-40% by volume	Similar (Predicate: 35 ± 10 um in diameter; 30-40% by volume) - While sizes differ, the document states "Functionally, the composition of both Silk Voice® and the predicate are equivalent."
Sterility: SAL 10-6	Provided sterile, SAL 10-6	Same
How supplied: Prefilled syringe	Prefilled syringe	Same
Delivery: Injection	Injection	Same
Implant duration: Long-term (>6 mo)	Long-term (>6 mo)	Same
Biocompatibility: Tested in accordance with ISO 10993-1	Tested in accordance with ISO 10993-1. Meets requirements for intended use for various tests (Subchronic Systemic Toxicity, Mouse Micronucleus, Gene mutation (AMES) assay, Intramuscular Implantation, Intracutaneous Reactivity, Sensitization, Pyrogenicity, Acute Systemic Toxicity, Cytotoxicity) for both syringe and accessory catheter.	Same standard applied
Syringe Leachables/Extractables: Compliance with ISO 10993-17 and 10993-18; Margin of safety > 1000.	Evaluated for leachables/extractables. Margin of safety determined to be > 1000 for adult males and females.	(No direct comparison to predicate stated, but meets the safety criterion)
Shelf Life Testing: Supports labeled expiration dating.	Performed.	(No direct comparison, but meets the criterion)
Bench Testing (Delivery System Mechanical Integrity):	Extrusion force testing passed. Catheter peak tensile force testing passed (meets ISO 10555-1:2013). Catheter leak testing passed (no signs of leakage).	(No direct comparison, but meets pre-established design input requirements)
Animal Study - Local Tissue Response & Migration: Comparable tissue responses (inflammation, neovascularization) and retention of particles.	Comparable tissue responses (inflammatory cell composition and neovascularization at injection site) as predicate. Demonstrated retention of particles at injection site.	Functionally comparable to predicate

2. Sample Size Used for the Test Set and Data Provenance

Test Set (Non-Clinical/Animal Study):
- Animal Model: Canine model.
- Sample Size: n=12 for Silk Voice®; n=12 for the predicate product. (Total 24 animals)
- Data Provenance: Not specified, but likely proprietary laboratory animal studies (prospective for the study duration). Country of origin is not mentioned.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

Not Applicable in the traditional sense for this device. Ground truth for the animal study (histology, gross pathology, imaging) would be established by veterinary pathologists or other trained personnel, but the specific number or their detailed qualifications are not provided in this summary. This is not an AI/ML device relying on human expert annotations for performance validation.

4. Adjudication Method for the Test Set

Not Applicable. This is not an AI/ML evaluation where human expert adjudication of output is needed. For the animal study, the assessment of gross pathology, histopathology, inflammation, and neovascularization would typically follow established veterinary pathology protocols, which may involve multiple evaluators for quality control, but a formal "adjudication method" as used in AI performance evaluation is not relevant here.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No. An MRMC study is relevant for evaluating the impact of an AI system on human reader performance in image interpretation. This device is an injectable medical implant; therefore, an MRMC study is not applicable.

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

Not Applicable. This is not an algorithm-based device. "Standalone performance" would refer to an AI's diagnostic accuracy without human intervention. This concept does not apply to an injectable medical device.

7. The Type of Ground Truth Used

For the non-clinical (pre-clinical) animal study, the "ground truth" for evaluating the tissue response and device retention was established through:
- Gross Pathology: Macroscopic observations of tissues.
- Histopathology: Microscopic examination of tissue samples, including scoring of inflammation and neovascularization.
- Imaging: Incremental imaging performed during the study (specific type not detailed).

8. The Sample Size for the Training Set

Not Applicable. This device is not an AI/ML algorithm that requires a training set. The "design" of the device is based on materials science and engineering principles, not machine learning model training.

9. How the Ground Truth for the Training Set was Established

Not Applicable. As there is no training set for an AI/ML algorithm, there is no ground truth establishment for such a set. The development of the Silk Voice® device itself relies on established scientific and engineering principles, and biocompatibility/performance testing data from animal models and bench studies to demonstrate safety and functional equivalency.

Summary

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November 8, 2018

Sofregen Medical, Inc. Anh Hoang, PhD Chief Scientific Officer 200 Boston Avenue, Suite 1100 Medford. MA 02155

Re: K180631

Trade/Device Name: Silk Voice® Regulation Number: 21 CFR 874.3620 Regulation Name: Ear, Nose, And Throat Synthetic Polymer Material Regulatory Class: Class II Product Code: MIX Dated: October 5, 2018 Received: October 9, 2018

Dear Anh Hoang:

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 devicerelated adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see

https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely yours.

for Malvina B. Eydelman, M.D. Director Division of Ophthalmic and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K180631

Device Name Silk Voice

Indications for Use (Describe)

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

Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)
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In accordance with 21 CFR 807.87(h) and 21 CFR 807.92, the 510(k) Summary for the Silk Voice Vocal Cord Medialization System is provided below.

SUBMITTER 1.

Sofregen Medical, Inc. 200 Boston Avenue, Suite 1100 Medford, MA 02155

Contact Person: Anh Hoang, Ph.D. Phone: 781-874-2356 Email: ahoang@sofregen.com Date Prepared: November 4th, 2018

DEVICE 2.

Name of Device: Silk Voice Common Name: System, Vocal Cord Medialization Classification Regulation: 21 CFR 874.3620 Regulatory Class: II Product Code: MIX Panel: Ear, Nose, and Throat

3. PREDICATE DEVICE

Predicate Device: BioForm Medical's Radiesse Laryngeal Implant (K070090)

DEVICE DESCRIPTION 4.

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INDICATIONS FOR USE 5.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS 6.

Silk Voice® is based on the same technical approach to tissue bulking and vocal fold medialization as the predicate. Both devices are provided sterile in prefilled syringes. Both devices feature a particle component suspended in an aqueous gel carrier.

	SOFREGEN's Silk Voice® -Subject Device	BioForm's Radiesse LaryngealImplant (K070090) -Predicate	Comparison
Intended Use	Vocal fold augmentation	Vocal fold augmentation	Same
Indication for Use	Silk Voice® is indicated for vocalfold medialization and vocal foldinsufficiency that may beimproved by injection of a softtissue bulking agent. Silk Voice®injection augments the size of thedisplaced or deformed vocal foldso that it may meet the opposingfold at the midline for improvedphonation. Vocal foldinsufficiency associated withserious aspiration difficulties maybe an urgent indication.	BioForm's Radiesse LaryngealImplant is indicated for vocal foldmedialization and vocal foldinsufficiency that may be improvedby injection of a soft tissue hulkingagent. Radiesse Laryngeal Implantinjection augments the size of thedisplaced or deformed vocal fold sothat it may meet the opposing foldat the midline for improvedphonation. Vocal fold insufficiencyassociated with serious aspirationdifficulties may be an urgentindication.	Same
Intended User	ENT Specialists	ENT Specialists	Same
Composition	Silk particles suspended in across-linked, aqueous formulationof HA; 30-40% particle byvolume	Calcium hydroxyapatite (CaHA)particles suspended in an aqueousformulation ofcarboxymethylcellulose (CMC); 30-40% by volume	Similar
Particle component	380 ± 46 um in diameter;30-40% by volume	35 ± 10 um in diameter;30-40% by volume	Similar
Sterility	Provided sterile, SAL 10-6	Provided sterile, SAL 10-6	Same
How supplied	Prefilled syringe	Prefilled syringe	Same
Delivery	Injection	Injection	Same
Implant duration	Long-term (>6 mo)	Long-term (>6 mo)	Same

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Biocompatibility	Tested in accordance with ISO 10993-1	Tested in accordance with ISO 10993-1	Same
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Silk Voice® is comprised of porous silk particles, suspended in an HA carrier. The predicate, Radiesse Laryngeal Implant, is comprised of CaHA particles in a CMC carrier. Both devices contain 30-40% particles by volume that function as long-term, bioresorbable, structural/bulking agents. Functionally, the composition of both Silk Voice® and the predicate are equivalent.

Both devices have been validated using in vivo models to evaluate safety and performance. Both systems have been tested in accordance with the ISO 10993 standard for biocompatibility testing.

Thus, the differences between the devices do not raise new questions of safety or effectiveness for the subject device.

NON-CLINICAL TESTING & PERFORMANCE DATA 7.

7.1. Biocompatibility

Silk Voice® was tested in accordance with ISO 10993-1:2009 Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process. The following tests were performed:

Silk Voice®-Filled Syringes	Accessory Catheter
• Subchronic Systemic Toxicity• Mouse Micronucleus• Gene mutation (AMES) assay• Intramuscular Implantation• Intracutaneous (Intradermal) Reactivity• Sensitization• Pyrogenicity• Acute Systemic Toxicity• Cytotoxicity	• Cytotoxicity• Sensitization• Primary Buccal Irritation• Pyrogenicity• Acute Systemic Toxicity

Biocompatibility test results show that Silk Voice® meets the requirements of ISO 10993 for its intended use.

7.2. Syringe Leachables/Extractables

The Sofregen Silk Voice syringe was evaluated for leachables/extractables in accordance with ISO 10993-17 and 10993-18. Extraction conditions included aqueous and organic solvents. Exhaustive chemical characterization was performed on the extracts to evaluate: metals, nonvolatile solvents, semi-volatile solvents, and volatile solvents after syringe manufacturing and sterilization.

A toxicological risk assessment was performed on the quantitative levels of extractables, and it was determined that the margin of safety is greater than 1000 for adult males and females.

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7.3. Shelf Life Testing

Shelf life testing (device and packaging) was performed to support labeled expiration dating for Silk Voice®.

7.4. Bench Testing

Bench testing to characterize the mechanical integrity of the Silk Voice® delivery system included:

Extrusion force testing is to assess the force required to extrude Silk Voice® through ● the delivery system
. Catheter peak tensile force testing to confirm that the connections of the finished accessory catheter can meet the minimum peak tensile force requirements from ISO 10555-1:2013
. Catheter leak testing to confirm that the finished accessory catheter is water tight (no signs of leakage) when an appropriate hydraulic pressure is applied.

All bench testing passed the acceptance criteria. The bench testing demonstrated that Silk Voice® delivery system meets pre-established design input requirements for its intended use.

7.5. Animal Study

Silk Voice® was evaluated for local tissue response and migration tendency in a canine model (n=12 Silk Voice; n=12 predicate product) for 12 months. Incremental imaging was performed during the study to evaluate the tissue at the site of injection. Final metrics at the end of study included gross pathology, histopathology of the vocal folds including scoring of inflammation and neovascularization, and histological evaluation of cervical lymph nodes for device migration.

Silk Voice® had comparable tissues responses, including inflammatory cell composition and neovascularization at the injection site, as compared to the predicate. Silk Voice® demonstrated retention of particles at the site of injection in the treated vocal fold.

CONCLUSION 8.

Based on the same indications for use (and intended use), device functionality, usage, and performance, the subject Silk Voice® is substantially equivalent to the predicate Radiesse Laryngeal Implant (K070090).

Regulation Number and Section

§ 874.3620 Ear, nose, and throat synthetic polymer material.

(a)
Identification. Ear, nose, and throat synthetic polymer material is a device material that is intended to be implanted for use as a space-occupying substance in the reconstructive surgery of the head and neck. The device is used, for example, in augmentation rhinoplasty and in tissue defect closures in the esophagus. The device is shaped and formed by the suregon to conform to the patient's needs. This generic type of device is made of material such as polyamide mesh or foil and porous polyethylene.(b)
Classification. Class II.