CryoX™ Vitrification Freeze Kit is intended for use in the vitrification of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

CryoX™ Vitrification Thaw Kit is intended for use in the thawing of virified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.

Device Description

CryoX™ Vitrification Freeze Kit is designed to facilitate dehydration of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos before vitrification via rapid cooling in liquid nitrogen. CryoX™ Vitrification Freeze Kit contains two solutions to be used sequentially during vitrification. Both solutions consist of Medium 199 (M199), human serum albumin (HSA) and gentamicin sulfate. They also contain varying levels of cryoprotectants, including dimethyl sulfoxide (DMSO), ethylene glycol (EG), and sucrose.

CryoX™ Vitrification Thaw Kt contains three solutions to be used sequentially during oocyte and embryo thawing procedures. All three solutions contain M199, HSA, and gentamicin sulfate. They also contain decreasing concentrations of cryoprotectant.

The five solutions in the CryoX™ Vitrification Freeze Kit and Thaw Kt are aseptically filtered and provided in 4.5 mLPETG vials. The solutions in these kits are single-use only. They have a shelf-life of 6 months when stored at 2-8℃

AI/ML Overview

The document you provided is a 510(k) Premarket Notification from the FDA for a device called "CryoX™ Vitrification Freeze Kit / Thaw Kit." It details the device's indications for use, comparison to a predicate device, and a summary of non-clinical performance testing.

Based on the provided text, here's the information regarding acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are the product specifications that were tested during shelf-life testing. The reported device performance is indicated by the statement that these specifications "were met at time 0 and after accelerated aging."

Parameter	Acceptance Criteria	Reported Device Performance
Appearance	Clean, transparent, pink; no impurities	Met (implicitly, as specifications were met)
pH (per USP <791>)	7.2-7.6	Met (implicitly, as specifications were met)
Osmolality (mOsmol/kg)	ES: 855~~1042 (1:2 dilution) VS: 1916~~2477 (1:2 dilution) TS: 1653~~2430 DS: 871~~1025 WS: 307~318	Met (implicitly, as specifications were met)
Sterility (per USP <71>)	No microbial growth	Met (implicitly, as specifications were met)
Bacterial Enodtoxin (per USP <85>)	< 0.5 EU/mL	Met (implicitly, as specifications were met)
Mouse Embryo Assay (1-Cell MEA)	≥ 80% embryos developed to expanded blastocyst at 96 hours	Met (implicitly, as specifications were met)

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

The document does not specify the sample size used for the test set for any of the performance tests (e.g., pH, osmolality, sterility, bacterial endotoxin, MEA).

The data provenance is from non-clinical performance testing conducted by the manufacturer, Zhejiang Horizon Medical Technology Co., Ltd. The document does not specify the country of origin of the data beyond the manufacturer's location in China, nor does it explicitly state whether the studies were retrospective or prospective, though performance testing for product validation is typically prospective.

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

The document does not mention the use of experts to establish ground truth for the performance tests. These tests are primarily laboratory-based measurements of chemical and biological properties according to established standards (e.g., USP, ASTM, FDA guidance). The Mouse Embryo Assay (MEA) results are quantitative and follow a specified threshold rather than expert consensus.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set. Since the tests are largely objective measurements against defined numerical or qualitative criteria (e.g., pH range, endotoxin limit, percentage of blastocyst development), human adjudication in the typical sense (e.g., 2+1 reading) is not applicable.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is typically conducted for diagnostic imaging devices or other AI-driven tools where human interpretation plays a significant role. The CryoX™ Vitrification Freeze Kit / Thaw Kit is a reproductive media product, and its evaluation focuses on its chemical and biological properties and performance in preserving and thawing oocytes/embryos, not on human interpretive tasks.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done

This question is not applicable to the device described. The CryoX™ Vitrification Freeze Kit / Thaw Kit is a biological reagent kit, not an algorithm or AI-driven device. Its performance is intrinsic to the chemical formulation and its biological effect on cells, not an algorithmic output.

7. The Type of Ground Truth Used

The ground truth for the performance tests is based on defined quantitative and qualitative specifications derived from established standards and biological efficacy requirements. For example:

pH, Osmolality, Bacterial Endotoxin: Numerical ranges or limits according to USP monographs.
Sterility: Absence of microbial growth as per USP <71>.
Mouse Embryo Assay (MEA): A specific developmental endpoint (≥ 80% expanded blastocyst development) at 96 hours, as per FDA guidance.
These are objective, rather than subjective, ground truths typically established by consensus or pathology.

8. The Sample Size for the Training Set

The concept of a "training set" is not applicable to this device. Training sets are relevant for machine learning or AI models. This product is a medical device in the category of reproductive media, and its development and validation involve formulation, manufacturing, and performance testing, not algorithmic training.

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

As the concept of a "training set" does not apply to this device, the question of how its ground truth was established is not applicable.

Summary

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May 11, 2023

Zhejiang Horizon Medical Technology Co., Ltd Wu Tang RA Supervisor Rom 219, 2nd floor, Building 9, 1303 Asia-Pacific Road, Dagiao Town. Nanhu District Jiaxing, Zhejiang 314006 China

Re: K223265

Trade/Device Name: CryoX™ Vitrification Freeze Kit / Thaw Kit Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: April 7, 2023 Received: April 7, 2023

Dear Wu Tang:

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.

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.

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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-regulatoryinformation/postmarketing-safety-reporting-combination-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 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 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

510(k) Number (if known) K223265

Device Name CryoX™ Vitrification Freeze Kit / Thaw Kit

Indications for Use (Describe)

CryoXTM Vitrification Freeze Kit is intended for use in the vitrification of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

CryoXTM Vitrification Thaw Kit is intended for use in the thawing of virified oocytes (MII), 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 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary K223265

I. SUBMITTER

Applicant:	Zhejiang Horizon Medical Technology Co., Ltd.
Address:	Room 219, 2nd floor, Building 9, 1303 Asia-Pacific Road, Daqiao Town,
	Nanhu District, Jiaxing City, Zhejiang Province, P. R. China.
Phone:	+86-21-38954600-59403
Fax:	+86-21-50801305
Contact Person:	Wu Tang, RA Supervisor
Email:	Wu.Tang@microport.com

Date Prepared: May 8, 2023

II. DEVICE

Trade Name:	CryoX™ Vitrification Freeze Kit / Thaw Kit
Common Name:	Assisted Reproduction Media
Regulation Name:	Reproductive Media and Supplements
Regulation Number:	884.6180
Product Code:	MQL (Media, Reproductive)
Regulatory Class:	II

III. PREDICATE DEVICE

Vit Kit- Freeze NX and Vit Kit- Warm NX (K190152) from FUJIFILM Irvine Scientific, Inc.

The predicate device has not been subject to a design-related recall.

DEVICE DESCRIPTION IV.

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INDICATIONS for USE V.

CryoX™ Vitrification Freeze Kt is intended for use in the vitrification of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.

CryoX™ Vitrification Thaw Kt is intended for use in the thawing of vitrified oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.

COMPARISON OF INTENDED USE AND TECHNOLOGICAL CHARACTERISTICS WITH VL 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	K223265Subject Device	K190152Predicate Device	Comparison
Indication for Use	CryoX™ VitrificationFreeze Kit is intended foruse in the vitrification ofoocytes (MII), pronuclear(PN) zygotes through day3 cleavage stage embryosand blastocyst stageembryos.CryoX™ Vitrification ThawKit is intended for use inthe thawing of vitrifiedoocytes (MII), pronuclear(PN) zygotes through day3 cleavage stage	Vit Kit - Freeze NX(Vitrification Freeze Kit)is intended for use in thevitrification of oocytes(MII) and pronuclear(PN) zygotes throughday 3 cleavage stageembryos and blastocyststage embryos.Vit Kit - Warm NX(Vitrification Warm Kit) isintended for use in thethawing of vitrifiedoocytes (MII) andpronuclear (PN) zygotes	There are differences inthe wording of theindications for usestatements for the subjectand predicate device;however, the intendeduses of the subject andpredicate devices are thesame.
Comparison Item	K223265Subject Device	K190152Predicate Device	Comparison
	embryos, and blastocyststage embryos.	through day 3 cleavagestage embryos andblastocyst stageembryos.
Conditions for Use	Prescription Use Only	Prescription Use Only	Same
Freeze Kit Formulation	M199 (HEPES buffer)Sucrose (0.5M)EG (7.5% 15%)DMSO (7.5% 15%)HSAGentamicin Sulfate	CSCM (HEPES andMOPS buffer)Trehalose (0.5M)EG (7.5% 15%)DMSO 7.5% 15%HSAGentamicinDextran SubstituteSupplementSodium Bicarbonate	Different: Theformulations of the subjectand predicate devices arenot the same. Differencesin device formulations donot raise differentquestions of safety andeffectiveness (S&E).
Thaw Kit Formulation	M199 (HEPES buffer)Sucrose (0.5 M, 1M)HSAGentamicin Sulfate	CSCM (HEPES andMOPS buffer)Trehalose (0.5M, 1.0M)HSAGentamicinDextran SubstituteSupplementSodium Bicarbonate	Different: Theformulations of the subjectand predicate devices arenot the same. Differencesin device formulations donot raise differentquestions of S&E.
pH	ES: 7.2-7.6VS: 7.2-7.6TS: 7.2-7.6DS: 7.2-7.6WS: 7.2-7.6	ES: 7.05 - 7.44VS: 7.05 - 7.44TS: 7.05 - 7.45DS: 7.05 - 7.45WS: 7.05 - 7.45	Different: The subjectdevice has a higher pHrange than the predicatedevice. These differencesin pH specifications do notraise different questions ofS&E.
Osmolality(mOsmol/kg)	ES: 855~~1042 (1:2dilution)VS: 1916~~2477 (1:2dilution)	ES: 1150 - 1550VS: 1220 - 1620TS: 1550 - 1900DS: 830 - 930	Different: The subjectdevice and predicatedevices have differences inosmolality specifications.
Comparison Item	K223265Subject Device	K190152Predicate Device	Comparison
	TS: 1653~~2430DS: 871~~1025WS: 307~318	WS: 265 - 300	These differences inosmolality specificationsdo not raise differentquestions of S&E.
Bacterial Endotoxin	< 0.5 EU/mL	≤ 0.6 EU/mL	Different: The subjectdevice has a lowerendotoxin specificationthan the predicate device.This difference inendotoxin specificationdoes not raise differentquestions of S&E.
Mouse Embryo Assay	1-Cell MEA: ≥ 80%embryos developed toexpanded blastocyst at 96hours.	1-Cell MEA: ≥ 80%expanded blastocystafter 96 hours in culture	Same
Sterilization Method	Aseptic Filtration	Aseptic Filtration	Same
Shelf-Life	6 months	12 months	Different: The subjectdevice has a shorter shelf-life than the predicatedevice. Differences inshelf-life do not raisedifferent questions of S&E

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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 table, 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.

SUMMARY OF NON-CLINICAL PERFORMANCE TESTING VII.

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.

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. Shelf-life testing was conducted to support a 6-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- 16:
- A Appearance: Clean, transparent, pink; no impurities
- pH per USP < 791> : 7.2-7.6
- Osmolality per USP <785>: 855~~1042 mOsmoVkg for ES (1:2 dilution); 1916-2477 mOsmoVkg for VS (1:2 dilution); 1653~~2430 mOsmoVkg for TS; 871~1025 mOsmoVkg for DS; 307-318 mOsmol/kg for WS
- A Sterility per USP < 71>: No microbial growth
- Bacterial endotoxin per USP <85>: < 0.5 EU/mL
- 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.

CONCLUSION VIII.

The results of the performance testing described above demonstrate that CryoX™ Vitrification Freeze Kit / Thaw Kt 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.