V-VITFREEZE is intended for use in the vitrification of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

V- VITWARM is intended for use in the thawing of vitrified of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

Device Description

V-VITFREEZE AND V-VITWARM include a set of five media intended for use in the vitrification and thawing of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos as part of InVitro Fertilization (IVF) procedures.

V-VITFREEZE (2mL vials) includes two media components, Equilibration Solution (ES) and Vitrification Solution (VS), containing the cryoprotectants ethylene glycol, trehalose (only in VS), and dimethyl sulfoxide. During the vitrification process, embryos are first exposed to ES and then to VS.

Using this methodology, the permeating cryoprotectants can replace water in the oocyte or PN through blastocyst stage embryos prior to vitrification and storage in liquid nitrogen.

V-VITWARM (4mL vials) is composed of three media used stepwise for thawing and removing cryoprotectants from vitrified oocytes and PN through blastocyst stage embryos. It is composed of Thawing Solution (TS), Diluent Solution (DS) and Washing Solution (WS).

The base medium for the vitrification and thawing media includes water, salts, buffering agents, minerals, chelating agents, energy substrates, amino acids, hydroxypropyl cellulose, polymeric substance, gentamicin, and phenol red. Cryoprotectants in the media include ethylene glycol, (7.5% in ES and 15% in VS), DMSO (7.5% in ES and 15% in VS), and trehalose in VS, TS, and DS.

The five solutions in the V-VITFREZE and V-VITWARM kit are aseptically filtered (storage vials sterilized by radiation) and provided in polypropylene vials with high density polyethylene screw caps. They have a shelf-life of 12 months when stored at 2-8℃. Media in the vials can be used for up to seven days after vial opening.

AI/ML Overview

This is an FDA 510(k) clearance letter for the V-VITFREEZE and V-VITWARM devices, which are reproductive media and supplements. The document describes the device, its intended use, and a comparison to a predicate device. It also summarizes non-clinical performance testing.

However, the provided text does not contain detailed acceptance criteria and the results of a specific study in the format requested (e.g., a table of acceptance criteria and reported device performance with statistical metrics like sensitivity, specificity, accuracy). It focuses on physical and biological characteristics of the media rather than performance metrics of an AI or diagnostic device.

Therefore, I cannot fulfill all parts of your request exactly as specified because the document does not describe the acceptance criteria and a study in the context of an AI or diagnostic device's performance in the way you've outlined.

The document does list certain specifications for the media and the tests conducted to ensure the media meets those specifications, which are a form of acceptance criteria for manufacturing and quality control. I will extract these details.

Here's the information that can be extracted relevant to acceptance criteria and testing, adapted to the context of the provided document:

1. Table of Acceptance Criteria and the Reported Device Performance (as per non-clinical testing of the media):

Test/Characteristic	Acceptance Criteria	Reported Device Performance (Implied by "met" without specific data)
Appearance	All solutions pink to rose color without precipitates	Met (demonstrated through shelf-life testing)
pH (WS, DS, TS)	7.20 - 7.45	Met (demonstrated through shelf-life testing)
pH (VS)	7.50 - 7.70	Met (demonstrated through shelf-life testing)
pH (ES)	7.30 - 7.60	Met (demonstrated through shelf-life testing)
Osmolality (ES)	2300-3100 mOsm/kg (1:10 dilution)	Met (demonstrated through shelf-life testing)
Osmolality (VS)	4600-6150 mOsm/kg (1:20 dilution)	Met (demonstrated through shelf-life testing)
Osmolality (TS)	1250-1600 mOsm/kg (1:4 dilution)	Met (demonstrated through shelf-life testing)
Osmolality (DS)	730-930 mOsm/kg (1:2 dilution)	Met (demonstrated through shelf-life testing)
Osmolality (WS)	240-300 mOsm/kg (No dilution)	Met (demonstrated through shelf-life testing)
Sterility	No microbial growth	Met (demonstrated through shelf-life testing and aseptic filtration/filling validation)
Bacterial Endotoxin	< 0.25 EU/mL	Met (demonstrated through shelf-life testing)
Mouse Embryo Assay	≥ 80% embryos developed to expanded blastocyst at 96 hours (1-Cell MEA)	Met (demonstrated through shelf-life testing)
Shelf-Life	12 months (product specifications met at time 0 and after accelerated aging)	Demonstrated (product specifications were met for 12 months)

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

Sample Size: The document does not specify exact sample sizes for each test listed (e.g., how many vials were tested for pH, how many mouse embryos were used). It refers to "shelf-life testing," "aseptic filtration and aseptic filling validation," etc., which are general statements of testing performed.
Data Provenance: Not specified in terms of country of origin or whether prospective/retrospective for these non-clinical tests. These are typically internal quality control and validation tests conducted by the manufacturer.

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

Not applicable. These are laboratory-based, non-clinical tests for reproductive media, not an AI or diagnostic device requiring expert interpretation of results. The "ground truth" is defined by established laboratory testing standards (e.g., USP monographs, ISO standards, FDA guidance).

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

Not applicable. This is for expert consensus in diagnostic or AI studies.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:

Not applicable. This document describes reproductive media, not an AI-assisted diagnostic device.

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

Not applicable. This document describes reproductive media.

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

The "ground truth" for the non-clinical tests are established by industry standards and regulatory requirements. For example:
- Chemical/Physical tests (pH, Osmolality, Appearance): Defined by analytical standard methods (e.g., USP monographs).
- Sterility: Defined by microbiological testing methods (e.g., USP <71>).
- Bacterial Endotoxin: Defined by Limulus Amebocyte Lysate (LAL) test standards (e.g., USP <85>).
- Mouse Embryo Assay (MEA): Defined by the specified FDA guidance for ART devices, where successful development of a certain percentage of embryos to expanded blastocyst within 96 hours is the benchmark.

8. The sample size for the training set:

Not applicable. This is not an AI/ML device, so there is no training set.

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

Not applicable.

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 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.

September 13, 2024

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

Re: K240176 Trade/Device Name: V-VITFREEZE and V-VITWARM Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Received: August 8, 2024

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.

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).

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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 Rue"). 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

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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

510(k) Number (if known) K240176

Device Name V-VITFREEZE and V-VITWARM

Indications for Use (Describe)

V-VITFREEZE is intended for use in the vitrification of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

V- VITWARM is intended for use in the thawing of vitrified of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CER 801 Subpart D)	□ Over-The-Counter Use (21 CER 801 Subpart C)

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510(k) Summary K240176

SUBMITTER I.

Applicant:	VITROMED GmbH
Address:	Raiffeisenstr. 15a, 40764 Langenfeld, Germany
Phone:	+49 2173-20041-30
Fax:	+49 2173-20041-58
Contact Person:	Deepesh Changat
Email:	qm@vitromed.com
Consultant Contact:	Greg Holland, Regulatory Specialists, Inc.
Email:	greg@regulatoryspecialists.com

Date Prepared: September 10, 2024

II. DEVICE

Trade Name:	V-VITFREEZE; V-VITWARM
Common Name:	Assisted Reproduction Media
Regulation Name:	Reproductive Media and Supplement
Regulation Number:	884.6180
Product Code:	MQL (Media, Reproductive)
Regulatory Class:	II

III. PREDICATE DEVICE

Vitrification Kit and Thawing Kit (K171748) from Kitazato Corporation. The predicate device has not been subject to a design-related recall.

DEVICE DESCRIPTION IV.

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Using this methodology, the permeating cryoprotectants can replace water in the oocyte or PN through blastocyst stage embryos prior to vitrification and storage in liquid nitrogen.

V. INDICATIONS for USE

V-VITFREEZE is intended for use in the vitrification of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

V-VITWARM is intended for use in the thawing of vitrified of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

VI. COMPARISON OF INTENDED USE AND TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

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

Comparison Item	K240176Subject Device	K171748Predicate Device	Comparison
Indication for Use	V-VITFREEZE is intendedfor use in the vitrification ofoocytes (MII), pronuclear(PN) zygotes through day 3	The Vitrification Kit isindicated for use in thepreparation, vitrification,and storage of oocytes(MII), pronuclear (PN)	There are differences inthe wording of theindications for usestatements for the subjectand predicate device;
Comparison Item	K240176Subject Device	K171748Predicate Device	Comparison
	cleavage stage embryos andblastocyst stage embryos.V-VITWARM is intended foruse in the thawing of vitrifiedof oocytes (MII), pronuclear(PN) zygotes through day 3cleavage stage embryos andblastocyst stage embryos.	zygotes through day 3cleavage stage embryos,and blastocyst stageembryos.The Thawing Kit isindicated for use in thepreparation and thawing ofvitrified oocytes (MII),pronuclear (PN) zygotesthrough day 3 cleavagestage embryos, andblastocyst stage embryos.	however, the intendeduses of the subject andpredicate device mediaare the same (i.e.,vitrification and warmingof oocytes and embryos).
Conditions for Use	Prescription Use Only	Prescription Use Only	Same
Kit components	V-VITFREEZE consists ofEquilibration Solution (ES)and Vitrification Solution(VS). V-VITWARM includesTS (Thawing Solution), DS(Dilution Solution) and WS(Washing Solution).	The Vitrification Kitincludes three mediacomponents, BasicSolution (BS),Equilibration Solution (ES)and Vitrification Solution(VS). The Vitrification Kitcomes prepackaged with 4Cryotop devices (CryotopCL, Cryotop SC, orCryotop US), and 2 ReproPlates.The Thawing Kit iscomposed of TS(Thawing Solution), DS(Dilution Solution) andWS (Wash Solution). TheThawing Kit comes pre-packaged with one Repro	The predicate deviceincludes an additionalbasic solution component,equipment to conduct theprocedure (plates), and aclosed cryopreservationstorage device that aredifferent than the subjectdevice. These differencesdo not raise differentquestions of S&E.
Comparison Item	K240176Subject Device	K171748Predicate Device	Comparison
		Plate, and two 35 mmdishes.
Freeze Kit Formulation	Base medium (see DeviceDescription section ofsummary) withcryoprotectants EthyleneGlycol, DMSO, andTrehalose	Medium 199, EthyleneGlycol, DMSO, Sucrose,Dextran SerumSupplement, Gentamicin	Different: Theformulations of thesubject and predicatedevices are not the same.Differences in deviceformulations do not raisedifferent questions ofsafety and effectiveness(S&E).
Thaw Kit Formulation	Base medium (see DeviceDescription section ofsummary) withcryoprotectant Trehalose	Medium 199; Sucrose,Dextran SerumSupplement, Gentamicin	Different: Theformulations of thesubject and predicatedevices are not the same.Differences in deviceformulations do not raisedifferent questions ofS&E.
pH	WS; DS; TS: 7.20 - 7.45VS: 7.50 - 7.70ES: 7.30 - 7.60	7.2-7.6	Different: The subjectdevice has a higher pHrange than the predicatedevice. These differencesin pH specifications donot raise differentquestions of S&E.
Osmolality (mOsm/kg)	ES - 2300-3100 (1:10dilution)VS: 4600-6150 (1:20dilution)TS: 1250-1600 (1:4 dilution)DS - 730-930 (1:2 dilution)WS - 240-300 (No dilution)	Not available publicly	Different: The subjectdevice and predicatedevices have differencesin osmolalityspecifications. Thesedifferences in osmolalityspecifications do not raise
Comparison Item	K240176Subject Device	K171748Predicate Device	Comparison
Bacterial Endotoxin	< 0.25 EU/mL	≤ 0.25 EU/mL	Same
Mouse Embryo Assay	1-Cell MEA: ≥ 80% embryosdeveloped to expandedblastocyst at 96 hours.	1-Cell MEA: ≥ 80%expanded blastocyst after96 hours	Same
Sterilization Method	Aseptic FiltrationVials are sterilized viaradiation	Aseptic FiltrationVials are sterilized viaradiation	Same
Shelf-Life	12 months	12 months	Same

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K240176 Page 4 of 6

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As shown in the table above, there are differences in the indications for use statements and technological characteristics of the subject and predicate devices. However, as stated in the differences in indications for use do not represent a new intended use and the differences in technological characteristics do not raise different questions of safety and effectiveness.

VII. SUMMARY OF NON-CLINICAL PERFORMANCE TESTING

The following studies have been conducted in support of the substantial equivalence to the predicate device.

Aseptic filtration and aseptic filling validation, per ISO 13408-1:2008 & A1:2013 and ISO 13408-● 2:2018.
Vial radiation sterilization, per ISO 11137-1:2006 (including: Amendment 1 (2013) and Amendment ● 2 (2018)) Sterilization of health care products - Radiation - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices and ISO 11137-2:2013 -Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose [Including Amendment 1 (2022)].
Shelf-life testing was conducted to support a 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:
- Appearance: All of the solutions should be pink to rose color without precipitates A
- pH per USP <791>: WS, DS, TS: 7.20 7.45; VS: 7.50 7.70; ES: 7.30 7.60

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≫ Osmolality per USP <785>: ES 2300-3100 mOsm/kg (1:10 dilution), VS: 4600-6150 mOsm/kg (1:20 dilution), TS: 1250-1600 mOsm/kg (1:4 dilution), DS - 730-930 mOsm/kg (1:2 dilution), WS - 240-300 mOsm/kg (No dilution)
Sterility per USP <71>: No microbial growth A
Bacterial endotoxin per USP <85>: < 0.25 EU/mL
A MEA per the 2021 FDA guidance Mouse Embryo Assay for Assisted Reproduction Technology Devices: 1-Cell MEA: ≥ 80% embryos developed to expanded blastocyst at 96 hours.
Transportation testing per ASTM D4169-22 and cap/seal leak testing using a method equivalent to ● USP <1207.2> on transportation-conditioned devices.

VIII. CONCLUSION

The results of the performance testing described above demonstrate that V-VITFREEZE and V-VITWARM kit is as safe and effective as the predicate device and supports 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.