The HSV Straw is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 Cell and blastocyst stage embryos.

Device Description

An embryo is vitrified using the HSV Straw by placing an embryo suspended in a 0.5ul All entrification solution solution in a curved polymeric spatula (Medical Grade. Styrene-Butadiene Copolymer). The curved spatula is inserted in an outer straw with a Styrene-Butadiene Coporymer). The open, proximal end of the straw is sealed by the user. The sealed, weighted unsal Chd. The open, promishar effect freezing-vitrification. The weighted straw seated straw is placed in liquid nitrogen for embryo storage. Thawing-rewarming: While the remains in liquid nitrogen, part of the outer tube is cut away. The curved spatial, distal tip tellians in inquir mirogen, part of the outer straw and immediately immersed in thawing solution where thawing and dilution of the remaining vitrification solution occur simultaneously.

AI/ML Overview

The provided text describes the HSV Straw, a cryopreservation device, and compares it to predicate devices for substantial equivalence. It does not contain information about a study with acceptance criteria and reported device performance in the format of a table as requested, nor does it detail AI-assisted studies or specific ground truth methodologies in the usual sense of clinical diagnostic devices.

However, based on the provided text, I can extract information related to the device's performance through various tests and a clinical study, which implicitly serve as "acceptance criteria" for regulatory clearance.

Here's an attempt to structure the available information, keeping in mind that some requested fields might not be directly applicable or explicitly stated in the document's context (e.g., AI-specific details, number of experts for ground truth, adjudication methods).

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the successful completion of the tests and studies presented for substantial equivalence. The "performance" is demonstrated by the device meeting these criteria (e.g., high embryo survival rates, absence of adverse effects).

Criteria Type (Implied)	Acceptance Criteria (Implied from predicate comparison and successful testing)	Reported Device Performance (HSV Straw)
Embryo Survival Rate (Mouse Embryo Assay - MEA)	90-100% survival rate for blastocysts at 96 hours. (Based on predicate performance and successful MEA testing)	90-100% survival at 96 hours
Endotoxin Level	<1 EU per unit	Consistently demonstrated <1 EU per unit
Sterility	Sterility maintained	Not explicitly quantified but implied by successful regulatory clearance and absence of adverse effects.
Mechanical Integrity	Performance under use conditions (e.g., handling, sealing, rewarming process integrity)	Mechanical testing demonstrated performance of the device under use conditions.
Cooling Rate	Comparable to or better than predicate devices, suitable for effective vitrification.	2,900°C/min (determined by laboratory measurement with microminiature temperature monitoring)
Rewarming Rate	Comparable to or better than predicate devices, suitable for effective rewarming.	25,000°C/min (determined by laboratory measurement with microminiature temperature monitoring)
Clinical Embryo Survival Rate (Human)	>80% post-vitrification/rewarming survival. (Implied acceptability based on successful study outcomes)	>80% post-vitrification/rewarming embryo survival in each of the three clinical centers.
Absence of Device Associated Adverse Effects	No device-associated adverse effects.	No device associated adverse effects were experienced by the study sites.
Protection from Nitrogen Contamination	Embryos protected from nitrogen contamination inside a sealed straw.	Design information demonstrated protection of embryos from nitrogen contamination.
Successful Pregnancies and Live Births	Successful use of vitrified embryos for pregnancies and live births.	The three centers had high levels of embryo survival after thawing and successfully used the vitrified embryos for pregnancies and live births.

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

Clinical Study Test Set:
- Sample Size: 473 vitrification cycles, utilizing 1509 human embryos.
- Data Provenance: The study was conducted in "three centers representing diverse approaches to assisted fertility". The geographical location (country of origin) is not explicitly stated, but the manufacturer is French (Cryo Bio System, Paris, France). Given the FDA submission, it's possible these centers were in the US or collaborating internationally. The study appears to be prospective as it describes the routine use and continued use of the device in these centers.
Mouse Embryo Assay (MEA):
- Sample Size: Not explicitly stated, but performed with "mouse blastocysts".
- Data Provenance: Laboratory testing, likely internal or contracted, provenance not specified beyond "laboratory". Retrospective/Prospective not applicable in the clinical sense.

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

This information is not explicitly provided in the document.

For the clinical study, "three centers" were involved. It is implicitly understood that fertility specialists, embryologists, and other qualified healthcare professionals at these centers would have assessed embryo survival and clinical outcomes. However, the exact number and detailed qualifications of specific experts establishing "ground truth" (e.g., for embryo viability assessment) are not specified.
For the MEA, embryologists or laboratory technicians would assess mouse embryo survival.

4. Adjudication Method for the Test Set

This information is not explicitly provided in the document. For embryo survival and clinical outcomes in the clinical study, it's likely standard clinical practice and consensus among the operating professionals at each center. There's no mention of a formal adjudication panel (e.g., 2+1, 3+1).

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

No. A Multi-Reader Multi-Case (MRMC) comparative effectiveness study, particularly one involving AI assistance, was not conducted or described. This document pertains to a cryopreservation device, not an image-reading or diagnostic AI system.

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

No. This is not an AI algorithm but a physical medical device. Therefore, a standalone algorithm-only performance study is not applicable.

7. The Type of Ground Truth Used

Clinical Study: "Ground truth" was established based on clinical outcomes (human embryo survival after vitrification/rewarming, successful pregnancies, and live births) as assessed by the participating fertility centers. These are objective clinical endpoints.
Mouse Embryo Assay (MEA): "Ground truth" was established by embryo viability assessment at 96 hours post-thaw.
Other Tests: Ground truth for endotoxin was based on quantitative laboratory measurements, and for mechanical testing, it was based on functional performance metrics. Cooling/rewarming rates were empirically measured.

8. The Sample Size for the Training Set

This concept is not applicable as this document describes a physical medical device submission, not an AI model requiring a training set. The clinical study described served as a test set for the device's performance.

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

Not applicable (see point 8).

Summary

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Manufacturer and Submitter

Cryo Bio System 29 Rue Tronchet Paris 75008 FRANCE

Contact Person

Anne Linda van Kappel, MSc, PhD Phone: 33-1-49-24-05-05 FAX: 33-1-49-24-05-01 e-mail: alvk@cryobiosystem-imv.com

DCT 6 2010

Date Prepared: 17 September 2010

Establishment Registration

Cryo Bio System Owner Operator Number: 9042657

Device Trade Name

HSV Straw

Device Generic Name

Cryopreservation straw

Device Classification and Product Code

Class II (Special Controls) per Final Rule, 63FR 48428, Docket number 97N-0335 21 CFR 884, Subpart G, 884.6160 Assisted Reproduction Labware

Product Code: MQK

Indications for Use

The HSV Straw is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 Cell and blastocyst stage embrvos.

Device Description and Principles of Operation for the HSV Straw

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Attribute	HSV StrawTM,CryoBio System	Curently marketed,previously FDA cleared,cryopreservation device.CryoTipTM, IrvineScientific, Irvine CA	Curently marketed,previously FDA cleared,cryopreservation device.Rapid-iTM, VitrolifeSweden AB, Gothenberg,Sweden
510(k) #	K092398	K041562	K090832
Indications for use	The HSV Straw is acryopreservation devicedesigned to contain, vitrify andmaintain 4-8 cell and blastocyststage human embryos.	The CryotipTM is acryopreservation device that isintended to be used to contain,freeze and maintain oocytesand/or embryos.	Rapid-iTM is a cryopreservationdevice indicated to be used tocontain, vitrify and maintain 4-8cell stage embryos.
Method of action(vitrification)	An embryo, suspended in a0.5ul drops of the finalvitrification solution, is placed inthe curved spatula. The curvedspatula is inserted in the outerstraw and the open end of thestraw sealed. The sealedstraw is placed in liquidnitrogen.	Embryo samples suspended inthe final vitrification solution areaspirated into a capillary tubeand seals are effected on eachside of the sample.Subsequently, the tube isimmersed in liquid nitrogen.	Prefreeze a straw with theopen end extending from theliquid nitrogen. A 10 nanoliterdrop of vitrification solutionholding an embryo is placed ina capillary sized through hole inthe stick. This, in turn, isinserted in the pre frozen strawin liquid nitrogen to effectfreezing of the embryo.Subsequently, the open end ofthe straw is sealed.
Cooling Rate1. Seenote	2,900°C/min	12,000°C/min	1,220°C/min
Method of action(rewarming)	While the distal tip of the outertube remains in liquid nitrogen,part of the outer tube is cutaway. The curved spatula,containing the cryopreservedembryo, is immersed inthawing solution where thawingand dilution in the thawingsolution occur simultaneously.	The capillary tube with sampleis removed from liquid nitrogenand placed in a temperaturecontrolled solution. Afterthawing, the tube is cut openand the embryo and vitrificationsolution are washed out into adilution solution.	While the distal end of thestraw remains in liquidnitrogen, cut the sealedproximal end of the straw.Withdraw the stick and directlyimmerse the stick/vitrified dropin warming media.
Rewarming Rate1See note	25,000°C/min	41,098°C/min	7,700°C/min
Materials in contactwith tissue(embryos)	Medical Grade Styrene-Butadiene Copolymer.	Medical grade polyvinylchloride straw.	Polymethyl methacrylate(PMMA) stick and a poly vinylchloride (PVC) straw.
Warming: Contactwith the warmingmedium	Direct immersion of sample inthe warming solution forsimultaneous thawing anddilution.	The sealed straw is firstimmersed in solution andwarmed/thawed. In a secondstep, the thawed sample isexpelled and diluted in thewarming solution.	Direct immersion of sample inthe warming solution forsimultaneous thawing anddilution.

Technological Characteristics of the HSV Straw Compared to Predicate Devices

Note: The cooling/heating performance of the CryoTip and HSV devices were determined by laboration in Note: The coolingheating performance of the Cryo rp and 1139 device was interest the publication.
with microminature temperature monitoring. Data for the Rapid-I device used with microminature temperature montioning. Data for na map purification and Warming Embryos Using
Tarankonov et al, 2009, Numerical Simulations Tarankonov et al, 2007, Numerical Unitations Deticles of the Conference 2009, Milan.
the Rapid-i™ Device, Proceedings of the COMSOL Conference 2009, Milan.

Premarket Notification Summary, K092398 Page 2 of 3

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Substantial Equivalence to Marketed Products

Predicate devices:

Cryotip, Irvine Scientific, Irvine CA, K041562

Rapid-i, Virtrolife Sweden AB, K090832

Clinical use of the HSV Straw was studied in three centers representing diverse approaches to assisted fertility (blastomeres vs blastocysts, multiple embryo transfers vs single embryo transfers, hormone induced cycles vs natural cycles, etc). A total of 473 vitrification cycles using 1509 embryos were captured in the study. Each of the three centers had post vitrification/rewarming embryo % survival of greater than 80%. No device associated adverse effects were experienced by the study sites and the centers continue to routinely use the device. The three centers had high levels of embryo survival after thawing and successfully used the vitrified embryos for pregnancies and live births.

The submission contains information demonstrating substantial equivalence between the devices. Test data in the submission include mouse embryo assay (MEA), endotoxin and sterility data, mechanical testing, and heating and cooling rate data. MEA testing with mouse blastocysts at 96 hours yielded 90-100% survival and endotoxin testing consistently demonstrated <1 EU per unit. Mechanical testing demonstrated the performance of the device under use conditions.

Design information included in the submission demonstrated that the curved form of the spatula, surface tension of the embryo containing drop and device dimensions and configuration provide a safe environment whereby the embryos are protected from nitrogen contamination inside a sealed straw.

When the HSV Straw is used in accordance with indications and instructions for use, the differences between the HSV Straw and predicate devices do not raise new questions of safety and effectiveness. The clinical studies of the HSV Straw and engineering and other tests did not identify any adverse effects. This conclusion is based on the performance data and specifications. It can be concluded that the intended use, material composition and scientific technology properties of the HSV Straw demonstrate that the device is as safe, as effective, and performs as well as or better than the identified, legally marketed predicate devices in the United States.

Premarket Notification Summary, K092398 Page 3 of 3

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Image /page/3/Picture/0 description: The image shows the seal of the Department of Health & Human Services - USA. The seal features an eagle-like bird with three lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002.

Cryo Bio System % Mr. David Balding Consultant 26552 Tampico Place MISSION VIEJO CA 92691

6 2010

Re: K092398 Trade Name: HSV Straw Regulation Number: 21 CFR $884.6160 Regulation Name: Assisted reproduction labware Regulatory Class: II Product Code: MOK Dated: September 17, 2010 Received: September 21, 2010

Dear Mr. Balding:

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. 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. 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

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adverse events) (21 CFR 803); 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Hubert Lenoir MD

Herbert P. Lerner, M.D., Director (Acting) Division of Reproductive, Gastro-Renal and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health.

Enclosure

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Indications for Use

510(k) Number (if known): K092398

Device Name: HSV Straw

Indications for Use: The HSV Straw is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 Cell and blastocyst stage embryos.

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Signature

n Sign-Off) of Reproductive, Gastro-Re · Page of

Regulation Number and Section

§ 884.6160 Assisted reproduction labware.

(a)
Identification. Assisted reproduction labware consists of laboratory equipment or supplies intended to prepare, store, manipulate, or transfer human gametes or embryos for in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), or other assisted reproduction procedures. These include syringes, IVF tissue culture dishes, IVF tissue culture plates, pipette tips, dishes, plates, and other vessels that come into physical contact with gametes, embryos or tissue culture media.(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, and clinical testing). The device, when it is a dish or plate intended for general assisted reproduction technology procedures, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.