HSV STRAW

K092398 · Cryo Bio System · MQK · Oct 6, 2010 · Obstetrics/Gynecology

Device Facts

• Record ID: K092398
• Device Name: HSV STRAW
• Applicant: Cryo Bio System
• Product Code: MQK · Obstetrics/Gynecology
• Decision Date: Oct 6, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6160
• Device Class: Class 2
• Attributes: Real-World Evidence

Real-World Evidence

Submission	Device	Sponsor	RWD Sources	RWE Use Summary	Key Tags
K092398 · Oct 6, 2010	HSV STRAW	Cryo Bio System	Multi-center clinical study of routine fertility treatment cycles	The study evaluated the performance of the HSV Straw in 473 vitrification cycles across three clinical centers, demonstrating embryo survival rates >80% and successful pregnancies/live births.	Embryo survival; Vitrification; Clinical study; Routine clinical use

Clinical Evidence

Study Design	Population	Comparator	Key Endpoints
Multi-center retrospective clinical study	Human embryos (4-8 cell and blastocyst stage) undergoing vitrification; Sample Size: 473 cycles (1509 embryos); Number of Sites: 3	Not applicable for this study	Embryo survival rate, pregnancy, and live birth

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.

Device Story

HSV Straw is a cryopreservation storage device for human embryos. Input: embryo suspended in 0.5ul vitrification solution. Operation: embryo placed in curved medical-grade styrene-butadiene copolymer spatula; spatula inserted into outer straw; proximal end sealed; straw immersed in liquid nitrogen for storage. Rewarming: distal tip remains in liquid nitrogen while outer tube is cut; curved spatula immersed directly in thawing solution for simultaneous thawing and dilution. Used in assisted reproduction laboratories by embryologists. Benefits: provides protected environment for embryo vitrification and storage, preventing nitrogen contamination. Output: cryopreserved embryo ready for clinical use.

Clinical Evidence

Clinical study conducted across three centers with 473 vitrification cycles and 1509 embryos. Primary endpoint: post-vitrification/rewarming embryo survival rate. Results: >80% survival across all centers; successful pregnancies and live births reported. No device-associated adverse effects. Bench testing included mouse embryo assay (MEA) with 90-100% survival at 96 hours, endotoxin levels <1 EU/unit, and mechanical testing.

Technological Characteristics

Material: Medical Grade Styrene-Butadiene Copolymer. Form factor: Curved spatula inserted into outer straw. Cooling rate: 2,900°C/min. Rewarming rate: 25,000°C/min. Principle: Vitrification via direct immersion in liquid nitrogen. Sterilization: Not specified. Connectivity: None (standalone).

Indications for Use

Indicated for containment and maintenance of human 4-8 cell and blastocyst stage embryos during vitrification procedures.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Cryotip (K041562)
• Rapid-i (K090832)

Submission Summary (Full Text)

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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: [phone] FAX: [phone] e-mail: [e-mail]

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

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.

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| Attribute | HSV StrawTM,<br>CryoBio System | Curently marketed,<br>previously FDA cleared,<br>cryopreservation device.<br>CryoTipTM, Irvine<br>Scientific, Irvine CA | Curently marketed,<br>previously FDA cleared,<br>cryopreservation device.<br>Rapid-iTM, Vitrolife<br>Sweden AB, Gothenberg,<br>Sweden |
|--------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) # | K092398 | K041562 | K090832 |
| Indications for use | The HSV Straw is a<br>cryopreservation device<br>designed to contain, vitrify and<br>maintain 4-8 cell and blastocyst<br>stage human embryos. | The CryotipTM is a<br>cryopreservation device that is<br>intended to be used to contain,<br>freeze and maintain oocytes<br>and/or embryos. | Rapid-iTM is a cryopreservation<br>device indicated to be used to<br>contain, vitrify and maintain 4-8<br>cell stage embryos. |
| Method of action<br>(vitrification) | An embryo, suspended in a<br>0.5ul drops of the final<br>vitrification solution, is placed in<br>the curved spatula. The curved<br>spatula is inserted in the outer<br>straw and the open end of the<br>straw sealed. The sealed<br>straw is placed in liquid<br>nitrogen. | Embryo samples suspended in<br>the final vitrification solution are<br>aspirated into a capillary tube<br>and seals are effected on each<br>side of the sample.<br>Subsequently, the tube is<br>immersed in liquid nitrogen. | Prefreeze a straw with the<br>open end extending from the<br>liquid nitrogen. A 10 nanoliter<br>drop of vitrification solution<br>holding an embryo is placed in<br>a capillary sized through hole in<br>the stick. This, in turn, is<br>inserted in the pre frozen straw<br>in liquid nitrogen to effect<br>freezing of the embryo.<br>Subsequently, the open end of<br>the straw is sealed. |
| Cooling Rate1. See<br>note | 2,900°C/min | 12,000°C/min | 1,220°C/min |
| Method of action<br>(rewarming) | While the distal tip of the outer<br>tube remains in liquid nitrogen,<br>part of the outer tube is cut<br>away. The curved spatula,<br>containing the cryopreserved<br>embryo, is immersed in<br>thawing solution where thawing<br>and dilution in the thawing<br>solution occur simultaneously. | The capillary tube with sample<br>is removed from liquid nitrogen<br>and placed in a temperature<br>controlled solution. After<br>thawing, the tube is cut open<br>and the embryo and vitrification<br>solution are washed out into a<br>dilution solution. | While the distal end of the<br>straw remains in liquid<br>nitrogen, cut the sealed<br>proximal end of the straw.<br>Withdraw the stick and directly<br>immerse the stick/vitrified drop<br>in warming media. |
| Rewarming Rate1<br>See note | 25,000°C/min | 41,098°C/min | 7,700°C/min |
| Materials in contact<br>with tissue<br>(embryos) | Medical Grade Styrene-<br>Butadiene Copolymer. | Medical grade polyvinyl<br>chloride straw. | Polymethyl methacrylate<br>(PMMA) stick and a poly vinyl<br>chloride (PVC) straw. |
| Warming: Contact<br>with the warming<br>medium | Direct immersion of sample in<br>the warming solution for<br>simultaneous thawing and<br>dilution. | The sealed straw is first<br>immersed in solution and<br>warmed/thawed. In a second<br>step, the thawed sample is<br>expelled and diluted in the<br>warming solution. | Direct immersion of sample in<br>the warming solution for<br>simultaneous thawing and<br>dilution. |

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 [phone] or [phone] 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