V-GRAD is a sterile colloidal suspension with silicate particles, stabilized with covalently bound hydrophilic silanes that is intended for separation of motile sperm from ejaculates by the density gradient method for use in assisted reproduction procedures. Available as a 100 % stock solution (V-GRAD 100) and as 40% or 80% ready-to-use solutions (V-GRAD 40 and V-GRAD 80) with HEPES buffered Human Tubular Fluid (HTF) medium. V-GRAD 100 is a stock solution for preparing a density gradient system for semen preparation. The V-GRAD Kit consists of two bottles of V-GRAD 40 and V-GRAD 80. V-GRAD is aseptically filtered and provided in pre-sterilized 12 mL glass bottles closed with flourotec rubber stoppers and flip-tear off caps or 100 mL PET(G) bottles closed with HDPE screw caps. V-GRAD has a shelf-life of one year when stored at 2-8°C and can be used for up to seven days after bottle opening.

AI/ML Overview

The provided text describes the regulatory clearance of a medical device, V-GRAD, which is a reproductive medium used for sperm separation. It outlines the device's technical specifications and compares them to a legally marketed predicate device (ORIGIO Gradient). However, the document primarily focuses on non-clinical performance testing to support substantial equivalence and does not contain information about acceptance criteria or a study proving the device meets those criteria in the context of an AI/human-in-the-loop system.

The device, V-GRAD, is a laboratory reagent (colloidal suspension for density gradient sperm separation), not an AI-powered diagnostic or assistive tool. Therefore, the concepts of "acceptance criteria" and "study" as typically applied to AI-driven medical devices (e.g., using a test set, expert ground truth, MRMC studies, standalone performance) are not applicable to the V-GRAD submission as described.

The "performance testing" mentioned in the document refers to traditional lab-based tests for reproductive media:

Aseptic filtration and aseptic filling validation: Ensures the sterility of the manufacturing process.
Shelf-life testing: Verifies that the product maintains its specifications (appearance, pH, osmolality, endotoxin, density, Human Sperm Survival Assay (HSSA), sterility) over its stated shelf life after accelerated aging and simulated use.
Transportation testing: Ensures the product integrity during shipping.
Sperm evaluation: Confirms that sperm separated using the device exhibit comparable motility, morphology, and purity to those separated with the predicate device.

Since the prompt asks for details related to AI/human-in-the-loop medical device evaluation, and the provided text does not describe such a device or study, I cannot fulfill the request using only the given input.

Therefore, for each point, the answer will be "Information not available in the provided text" or "Not applicable as the device is not an AI/human-in-the-loop system."

Based on the provided text, here is the information:

A table of acceptance criteria and the reported device performance

Acceptance Criteria and Reported Device Performance: The document lists "product specifications" that are met during shelf-life testing, which implicitly serve as acceptance criteria for the quality and performance of the medium itself. These are not performance metrics for an AI system.

Criteria/Specification	Acceptance Limit (Implied)	Reported Performance (Implied, "met specifications")
Appearance	Pink rose (V-GRAD 40), light pink (V-GRAD 80), colorless (V-GRAD 100)	Met
pH	7.2-7.9	Met
Osmolality (mOsm/kg)	310-340 (V-GRAD 40/80), 300-330 (V-GRAD 100)	Met
Endotoxin (EU/mL)	<0.5	Met
Density (g/cm³)	1.050-1.061 (V-GRAD 40), 1.100-1.111 (V-GRAD 80), 1.125-1.136 (V-GRAD 100)	Met
Human Sperm Survival Assay (HSSA)	≥ 80% of control motility at 24 hours after 1-hour exposure to test medium	Met
Sterility (USP <71>)	No growth	Met
Sperm Evaluation (Motility, Morphology, Purity)	Comparable performance with predicate device and other cleared devices	Demonstrated comparable performance
Shelf-Life	1 Year	Supported (met specifications at time 0 and after accelerated aging)

Sample sizes used for the test set and the data provenance: Information not available in the provided text. The studies described are non-clinical lab tests of the medium itself, not a clinical test set for an AI device.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable as the device is not an AI/human-in-the-loop system requiring expert-adjudicated ground truth. The "ground truth" for V-GRAD's performance is established by standardized laboratory assays (e.g., pH meters, osmometers, endotoxin testing, HSSA).
Adjudication method (e.g. 2+1, 3+1, none) for the test set: Not applicable as the device is not an AI/human-in-the-loop system.
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 as the device is not an AI/human-in-the-loop system.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not applicable as the device is not an AI/human-in-the-loop system.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.): For the performance of the V-GRAD medium, the "ground truth" is defined by established laboratory methods and controls for measuring characteristics like pH, osmolality, sterility, and the biological response in an HSSA. For "Sperm separated using the subject device were evaluated for motility, morphology, and purity," the ground truth would be the measurement outcomes from standard semen analysis techniques, compared to controls (predicate device or other cleared devices).
The sample size for the training set: Not applicable as the device is not an AI/machine learning system.
How the ground truth for the training set was established: Not applicable as the device is not an AI/machine learning system.

Summary

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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 consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

March 21, 2025

VITROMED GmbH c/o Greg Holland Sr. Partner Regulatory Specialists, Inc. 3722 Ave. Sausalito Irvine, California 92606

Re: K241833 Trade/Device Name: V-GRAD (V-GRAD Kit, V-GRAD 40, V-GRAD 80, V-GRAD 100) Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MOL Received: February 19, 2025

Dear Greg Holland:

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.

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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 (QS) 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 mediation-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

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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,

Michael T. Bailey -S

For Monica D. Garcia, Ph.D. Assistant Director DHT3B: Division of Reproductive, Gynecology, and Urology Devices OHT3: Office of Gastrorenal, ObGyn, General Hospital, and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 07/31/2026 See PRA Statement below.

Submission Number (if known)

K241833

Device Name

V-GRAD (V-GRAD Kit, V-GRAD 40, V-GRAD 80, V-GRAD 100)

Indications for Use (Describe)

V-GRAD is intended for separation of motile sperm from ejaculates by the density gradient method for use in assisted reproduction procedures.

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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510(k) Summary
K241833

510(k) Owner	VITROMED GmbHRaiffeisenstr. 15a40764 LangenfeldGermanyPhone: +49 2173-20041-30Facsimile: +49 2173-20041-58Contact: Ines DienerEmail: ines@vitromed.com
Submission Correspondent	Greg HollandRegulatory Specialists, Inc.3722 Ave. SausalitoIrvine, CA 92606Phone: 949.262.0411Fax: 949.552.2821Email: greg@regulatoryspecialists.com
Summary Date	March 21, 2025
Trade Name	V-GRAD (V-GRAD Kit, V-GRAD 40, V-GRAD 80, V-GRAD 100)
Common Name	Assisted Reproduction Media
Classification Name	Reproductive Media and Supplements
Regulation	884.6180
Class	Class II
Product Code	MQL (Media, Reproductive)
Predicate Device	K153267ORIGIO A/SORIGIO Gradient 100, ORIGIO Gradient 90, ORIGIOGradient 40/80The predicate device has not been subject to adesign-related recall.

Device Description

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V-GRAD 100 is a stock solution for preparing a density gradient system for semen preparation. The V-GRAD Kit consists of two bottles of V-GRAD 40 and V-GRAD 80.

V-GRAD is aseptically filtered and provided in pre-sterilized 12 mL glass bottles closed with flourotec rubber stoppers and flip-tear off caps or 100 mL PET(G) bottles closed with HDPE screw caps. V-GRAD has a shelf-life of one year when stored at 2-8°C and can be used for up to seven days after bottle opening.

Indications for Use

V-GRAD is intended for separation of motile sperm from ejaculates by the density gradient method for use in assisted reproduction procedures.

Comparison of the Subject and Predicate Device Intended Use and Technological Characteristics

A comparison of the intended use and technological features of the subject and predicate devices are described in the table below:

	K241833V-GRAD (V-GRAD KitV-GRAD 40, V-GRAD80, V-GRAD 100)	K153267ORIGIO Gradient100, ORIGIOGradient 90,ORIGIO Gradient40/80	Comparison
Indications forUse	V-GRAD is intendedfor separation ofmotile sperm fromejaculates by thedensity gradientmethod for use inassisted reproductionprocedures.	ORIGIO® Gradient™ 100, ORIGIO®Gradient™ 90 andORIGIO® Gradient™40/80 are for theseparation of motilesperm from theejaculate by thedensity gradientmethod.	There aredifferences in thewording of theindications for usestatements for thesubject andpredicate device;however, both havethe same intendeduse, i.e., separationof motile sperm fromthe ejaculates by thedensity gradientmethod.
Conditions forUse	Prescription Use Only	Prescription Use Only	Same
	K241833V-GRAD (V-GRAD KitV-GRAD 40, V-GRAD80, V-GRAD 100)	K153267ORIGIO Gradient100, ORIGIOGradient 90,ORIGIO Gradient40/80	Comparison
AvailableVariants	- V-GRAD 100- V-GRAD 40- V-GRAD 80- V-GRAD Kit(containing V-GRAD 80 and V-GRAD 40)	- ORIGIOGradient™ 100- ORIGIOGradient™ 90- ORIGIOGradient™ 40/80	Different: There aredifferences in themedium variants forthe subject andpredicate devices;however, thesedifferences do notraise differentquestions of S&E.
GradientMediumDensity (%silica)	40%, 80%, 100%	40%, 80%, 90%, 100%	Different: Thegradient mediumdensity for thesubject andpredicate devices isdifferent; however,this difference doesnot raise differentquestions of S&E.
Formulation	Physiological salts;energy substrates;buffering agents;silane-coated silica;gentamicin sulfate;phenol red; water	Not known	Different: Theformulation of thepredicate device isnot known; however,the differences inmedia productformulations do notraise differentquestions of S&E
Sterilization	Aseptic filtration	Aseptic filtration	Same
Sterility	No growth	No growth	Same
pH	7.20 – 7.90	7.95 – 8.495	Different: Thesubject device has alower pH range thanthe predicate device.This difference in pHrange does not raisedifferent questionsof S&E.
	K241833V-GRAD (V-GRAD KitV-GRAD 40, V-GRAD80, V-GRAD 100)	K153267ORIGIO Gradient100, ORIGIOGradient 90,ORIGIO Gradient40/80	Comparison
Endotoxin(EU/ml)	<0.5	<0.8	Different: Thesubject device has alower endotoxinlevel than thepredicate device.This difference inendotoxinspecifications doesnot raise differentquestions of S&E.
Osmolality(mOsm/kg)	310-340 (V-GRAD 40)310-340 (V-GRAD 80)300-330 (V-GRAD100)	317-333 (OrigioGradientTM 40)297-313 (OrigioGradientTM 80, 90 and100)	Similar
Density (g/cm3)	1.050-1.061 (V-GRAD40)1.100-1.111 (V-GRAD80)1.125-1.136 (V-GRAD100)	1.048-1.062 (OrigioGradientTM 40)1.098-1.112 (OrigioGradientTM 80)1.105-1.119 (OrigioGradientTM 90)1.123-1.137 (OrigioGradientTM 100)	Similar
Storage	2-8°C	2-8°C	Same
HSSA	≥ 80% of controlmotility at hours after 1hour exposure to testmedium	≥ 80% of control	Different: TheHSSA exposure timefor the predicatedevice is not known;however, thisdifference does notraise differentquestions of S&E.
Shelf Life	1 Year	20 weeks (Origio 100)36 weeks (Origio 40,80, and 90)	Different: Thesubject device has alonger shelf life thanthe predicate device.Difference does notraise differentquestions of S&E

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As shown in the table above, there are differences in the indications for use statements and technological features of the subject and predicate devices. However, the subject and predicate device have the same intended use and the differences in technological features do not raise different questions of safety and effectiveness.

Summary of Non-Clinical Performance Testing

The following studies have been performed to support substantial equivalence to the predicate device:

. Aseptic filtration and aseptic filling validation, per ISO 13408-1:2008 - Aseptic Processing of Health Care Products – Part 1 General Requirements (including Amendment 1 (2013)) and ISO 13408- 2:2018 – Aseptic Processing of Health Care Products - Part 2 Sterilizing Filtration.
Shelf-life testing was conducted to support the 12-month shelf-life for the subject . device through demonstration that the product specifications (shown below) were met at time 0 and after accelerated aging in accordance with ASTM F1980-21. Testing was also included on aged samples demonstrating that medium in bottles can maintain their specifications after seven days of simulated use conditioning after bottle opening. Testing conducted is shown below:
- Appearance: Pink rose color (V-GRAD 40), light pink color (V-GRAD 80), colorless (V-GRAD 100)
- pH: 7.2-7.9
- Osmolality (mOsm/kg): 310-340 (V-GRAD 40 and V-GRAD 80), 300-330 (V--GRAD 100)
- -Endotoxin (EU/mL): <0.5
- Density (g/cm³): 1.050-1.061 (V-GRAD 40), 1.100-1.111 (V-GRAD 80), 1.125--1.136 (V-GRAD 100)
- Human Sperm Survival Assay (HSSA): ≥ 80% of control motility at 24 hours after -1 hour exposure to test medium
- -Sterility, per USP <71>: No growth
. Transportation testing per ASTM D4169-22 and USP <1207.2>.
. Sperm separated using the subject device were evaluated for motility, morphology, and purity. The results demonstrate that the subiect device has comparable performance with the predicate device and other cleared devices of this type.

Conclusions

The results of the performance testing described above demonstrate that V-GRAD is as safe and effective as the predicate device and support a determination of substantial equivalence.

Regulation Number and Section

§ 884.6180 Reproductive media and supplements.

(a)
Identification. Reproductive media and supplement are products that are used for assisted reproduction procedures. Media include liquid and powder versions of various substances that come in direct physical contact with human gametes or embryos (including water, acid solutions used to treat gametes or embryos, rinsing solutions, sperm separation media, supplements, or oil used to cover the media) for the purposes of preparation, maintenance, transfer or storage. Supplements are specific reagents added to media to enhance specific properties of the media (e.g., proteins, sera, antibiotics, etc.).(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, biocompatibility testing, and clinical testing). The device, when it is phosphate-buffered saline used for washing, and short-term handling and manipulation of gametes and embryos; culture oil used as an overlay for culture media containing gametes and embryos; and water for assisted reproduction applications, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.