RapidVit™ Cleave is used for vitrification of day 3 cleavage stage embryos. The cryoprotectants 1,2-propanediol and ethylene glycol are used together with sucrose for dehydration of the embryo before cryopreservation. Then the embryos are immediately plunged into liquid nitrogen in order to prevent intracellular and extracellular ice crystal formation.

RapidWarm™ Cleave is used for the subsequent warming of vitrified day 3 cleavage stage embryos

AI/ML Overview

The provided document is limited in the detail required to populate all fields of the request. The submission is a 510(k) premarket notification for a medical device, which primarily focuses on demonstrating substantial equivalence to a predicate device rather than presenting a detailed study with extensive performance metrics and ground truth establishment.

Here's a breakdown of what can be extracted and what information is missing:

1. Table of acceptance criteria and the reported device performance:

Acceptance Criteria	Reported Device Performance
Not explicitly stated in terms of quantitative criteria or success rates in this document.	"Successful vitrification of human cleavage stage embryos by use of RapidVit™ Cleave and RapidWarm™ Cleave has been clinically proven (Balaban et al. 2008)."
Substantial equivalence to predicate device (Vit Kit™ - Freeze and Vit Kit™ - Thaw)	The FDA determined the device is substantially equivalent to legally marketed predicate devices.

Missing Information: Specific quantitative acceptance criteria (e.g., survival rate, viability rate, developmental rate post-vitrification/warming) are not detailed in this 510(k) summary. The document states that successful vitrification has been "clinically proven" by a referenced study (Balaban et al. 2008), but the performance metrics from that study are not included in this document.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective):

Sample Size for Test Set: Not mentioned in this 510(k) summary. The summary refers to a clinical study by "Balaban et al. 2008" but does not provide details about its sample size.
Data Provenance: Not mentioned in this 510(k) summary. The country of origin and whether the study was retrospective or prospective are not specified.

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

Number of Experts: Not applicable, as this device (vitrification/warming kit for embryos) does not involve expert interpretation for ground truth in the way diagnostic imaging algorithms do. Ground truth for embryo vitrification/warming studies typically involves objective biological outcomes.
Qualifications of Experts: N/A

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

Adjudication method: Not applicable. Similar to point 3, this type of device study does not typically involve adjudication of expert opinions for ground truth.

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:

MRMC Study: No, an MRMC study was not done. This type of study design is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) and AI assistance. This device is a biological solution for embryo cryopreservation.
Effect size of human reader improvement with AI: N/A

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

Standalone Performance: Not applicable. This device is a chemical solution used in a clinical procedure. It is not an algorithm, and therefore, "standalone" performance in the context of an algorithm does not apply. The device's performance is inherently tied to its use in a human-orchestrated process (embryo vitrification and warming).

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

Type of Ground Truth: The document refers to "clinical proven" results from the Balaban et al. 2008 study. For embryo vitrification and warming, the ground truth would typically be based on objective biological outcomes such as:
- Embryo survival rates post-warming
- Embryo developmental rates (e.g., reaching blastocyst stage)
- Pregnancy rates
- Live birth rates
  The specific outcomes used as ground truth for the "clinically proven" statement are not detailed in this 510(k) summary but would be found in the referenced publication.

8. The sample size for the training set:

Sample Size for Training Set: Not applicable. This device is a chemical kit, not an AI/ML algorithm that requires a training set. The "training" in this context would be pre-clinical testing and manufacturing quality control, not data-driven model training.

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

Ground Truth Establishment for Training Set: Not applicable, as explained in point 8.

Summary

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K 080446

X. PREMARKET NOTIFICATION SUMMARY

NOV 2 6 2008

	NOV 26 2008
Submitted by:	Vitrolife Sweden ABBox 9080SE-400 92 GöteborgSWEDEN
Contact Person:	Mr Kjell KjörkVitrolife Sweden ABBox 9080SE-400 92 GöteborgSWEDENPhone +46 31 721 80 77Fax +46 31 721 80 90Mail kkjork@vitrolife.com
Date Prepared:	25 November 2008
Trade Name:	RapidVit™ CleaveRapidWarm™ Cleave
Common Name:	Vitrification freeze kit for cleavage stage embryosVitrification warming kit for cleavage stageembryos
Classification Name:	Reproductive Media and Supplements(21 C.F.R. § 884.6180)
Predicate Device:	Vit Kit™ - Freeze and Vit Kit™ - Thaw from IrvineScientific Co., Inc. (K060168)
Description of the Device:	RapidVit™ Cleave is used for vitrification of day 3cleavage stage embryos. The cryoprotectants 1,2-propanediol and ethylene glycol are used togetherwith sucrose for dehydration of the embryo beforecryopreservation. Then the embryos are

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immediately plunged into liquid nitrogen in order to prevent intracellular and extracellular ice crystal formation.

RapidWarm™ Cleave is used for the subsequent warming of vitrified day 3 cleavage stage embryos

Intended Use:

Rapid Vit™ Cleave is intended for vitrification of day 3 cleavage stage embryos

RapidWarm™ Cleave is intended for warming of vitrified day 3 cleavage stage embryos

Technological Characteristics:

RapidVit™ Cleave and RapidWarm™ Cleave are devices used for vitrification of day 3 cleavage stage embryos. The cryoprotectants 1,2-propanediol and ethylene glycol are

used together with sucrose for dehydration of the embryo before cryopreservation. Then the embryos are immediately plunged into liquid nitrogen in order to prevent intracellular and extracellular crystal formation.

The predicate device Vit Kit™ - Freeze/Vit Kit™ - Thaw and RapidVit™ Cleave/RapidWarm™ Cleave are embryo-physiological solutions supplemented with permeable and non-permeable cryoprotectants. Both devices are subject to the same control methods and, to a significant degree, contain the same components. They have similar handling procedures and the same sterility assurance level (10") and storage conditions.

The main differences between RapidVit™ Cleave and RapidWarm™ Cleave and Vit Kit™ - Freeze and Vit Kit™ - Thaw are the following:

Vit Kit™ Freeze and Vit Kit™ Thaw contain ethylene glycol, DMSO and . sucrose as cryoprotectants, while RapidVit™ Cleave and RapidWarm™ Cleave contain ethylene glycol, 1,2-propanediol and sucrose
Vit Kit™ Freeze and Vit Kit™ Thaw is intended for blastocysts stage . embryos while RapidVit™ Cleave and RapidWarm™ Cleave is intended for cleavage stage embryos

Successful vitrification of human cleavage stage embryos by use of RapidVit™ Cleave and RapidWarm™ Cleave has been clinically proven (Balaban et al. 2008).

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of three overlapping shapes resembling a person with outstretched arms, positioned to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the graphic.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. Kjell Kjörk Pharmacist, Regulatory Affairs Manager Vitrolife Sweden AB Faktorvägen 13 SE-434 37 Kungsbacka SWEDEN

NOV 26 2006

K080446 Re:

Trade/Device Name: RapidVit™ Cleave RapidWarm" Cleave Regulation Number: 21 CFR §884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: II Product Code: MQL Dated: November 10, 2008 Received: November 12, 2008

Dear Mr. Kjörk:

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. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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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Page 2

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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at one of the following numbers, based on the regulation number at the top of this letter:

21 CFR 876.xxx	(Gastroenterology/Renal/Urology)	240-276-0115
21 CFR 884.xxx	(Obstetrics/Gynecology)	240-276-0115
21 CFR 894.xxx	(Radiology)	240-276-0120
Other		240-276-0100

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometrics' (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers. International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jozpu M. Whang

Joyce M. Whang, Ph.D. Acting Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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K080446

XI. INDICATIONS FOR USE STATEMENT

510(k) Number (if known):

K080446

Device Name:

RapidVit™ Cleave RapidWarm™ Cleave

Indications for Use:

RapidVit™ Cleave is indicated for vitrification of day 3 cleavage stage embryos

RapidWarm™ Cleave is indicated for warming of vitrified day 3 cleavage stage embryos

RapidVit™ Cleavage and RapidWarm™ Cleavage are restricted to sale by or on the order of a physician.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 C.F.R. § 801.109)

Over-the Counter Use

(Division Sign-Off) (Division of Reproductive, Abdominal and Radiological Devices 510(k) Number

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.