Vitrification Kit and Thawing Kit

K171748 · Kitazato Corporation · MQL · Dec 14, 2017 · Obstetrics/Gynecology

Device Facts

• Record ID: K171748
• Device Name: Vitrification Kit and Thawing Kit
• Applicant: Kitazato Corporation
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Dec 14, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

The Vitrification Kit is indicated for use in the preparation, vitrification and storage of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos. The Thawing Kit is indicated for use in the preparation and thawing of vitrified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.

Device Story

Vitrification and Thawing Kits consist of chemical media for cryopreservation of human oocytes and embryos; used in ART clinics by embryologists. Vitrification process: sequential exposure of samples to Basic Solution (BS), Equilibration Solution (ES), and Vitrification Solution (VS) containing ethylene glycol, trehalose, and DMSO; cryoprotectants replace water in samples; samples loaded onto Cryotop devices and stored in liquid nitrogen. Thawing process: sequential exposure to Thawing Solution (TS), Dilution Solution (DS), and Wash Solution (WS) to remove cryoprotectants. Media contain Gentamicin. Output is cryopreserved or thawed viable reproductive cells/embryos for subsequent IVF procedures. Benefits include successful long-term storage and recovery of embryos/oocytes for future fertility treatments.

Clinical Evidence

Clinical evidence provided via literature review of studies using media with similar formulations (HPC-based). Studies (Coello et al. 2016, Mori et al. 2015, Inoue et al. 2014) demonstrate comparable oocyte/embryo survival rates, implantation rates, clinical pregnancy rates, and live birth rates to predicate-style vitrification methods. Bench testing included sterilization validation, packaging validation, and performance testing (Mouse Embryo Assay >80% development).

Technological Characteristics

Media components: Medium 199 HEPES-buffered, ethylene glycol, DMSO, trehalose, hydroxypropyl cellulose (HPC), and gentamicin. Storage devices (Cryotop) sterilized by radiation; media sterilized by aseptic filtration. Storage at 2–8°C. Shelf life: 1 year. Endotoxin <0.25 EU/mL. pH 7.20–7.60.

Indications for Use

Indicated for preparation, vitrification, and thawing of human oocytes (MII), pronuclear (PN) zygotes, cleavage stage embryos (up to day 3), and blastocyst stage embryos for ART procedures.

Regulatory Classification

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.).

Special Controls

*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.

Predicate Devices

• Vit Kit® - Vitrification Freeze Kit/ Vitrification Thaw Kit (K160006)

Reference Devices

• Cryotop®CL (K112695)
• Cryotop®SC (K140072)
• Cryotop®US (K153027)
• HSV Straw (K092398)
• CryoTip (K041562)

Submission Summary (Full Text)

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December 14, 2017

Kitazato Corporation % Diane Sudduth Senior Consultant, RA Emergo Global Consulting, LLC 2500 Bee Cave Road, Building 1, Suite 300 Austin, TX 78746

Re: K171748

Trade/Device Name: Vitrification Kit and Thawing Kit Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MOL, MOK Dated: November 9, 2017 Received: November 13, 2017

Dear Diane Sudduth:

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.

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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); 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.

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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

# Joyce M. Whang -S

for Benjamin R. Fisher, Ph.D. Director 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) K171748

Device Name Vitrification Kit and Thawing Kit

Indications for Use (Describe)

The Vitrification Kit is indicated for use in the preparation, vitrification and storage of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.

The Thawing Kit is indicated for use in the preparation and thawing of vitrified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.

| Type of Use (Select one or both, as applicable) | |
|------------------------------------------------------------|-----------------------------------------------------------|
| <span></span> Prescription Use (Part 21 CFR 801 Subpart D) | <span></span> Over-The-Counter Use (21 CFR 801 Subpart C) |

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## 510(k) Summary

## Vitrification Kit and Thawing Kit

## K171748

#### 1. Submission Sponsor

Kitazato Corporation

81 Nakajima, Fuji-city

Shizuoka 416-0907

JAPAN

Phone number: +(81) 546-66-2202

Contact: Futoshi INOUE

Title: President

#### 2. Submission Correspondent

Emergo Global Consulting, LLC

2500 Bee Cave Road, Building 1, Suite 300

Austin, TX 78746

Office Phone: [phone]

Contact: Diane Sudduth, Senior Consultant, RA

Email: [e-mail]

#### 3. Date Prepared

14 December 2017

#### 4. Device Identification

| Trade/Proprietary Name: | Vitrification Kit and Thawing Kit |
|-------------------------|--------------------------------------|
| Common/Usual Name: | Vitrification Cryopreservation Media |
| Classification Name: | Reproductive Media and Supplements |
| Classification Number: | 884.6180 |

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| Product Code: | MQL - Media, Reproductive |
|-----------------------|--------------------------------------|
| | MQK – Labware, Assisted Reproduction |
| Device Class: | Class II |
| Classification Panel: | Obstetrics/Gynecology |

#### 5. Legally Marketed Predicate Devices

K160006, Vit Kit® - Vitrification Freeze Kit/ Vitrification Thaw Kit, Irvine Scientific Sales Co., Inc.

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

#### Device Description 6.

The Vitrification and Thawing Kits are composed of a set of six media to vitrify and warm MII oocytes, and pronuclear (PN) zygotes through blastocyst stage embryos for Assisted Reproductive Technology (ART) procedures.

The Vitrification Kit includes three media components, Basic Solution (BS), Equilibration Solution (ES) and Vitrification Solution (VS), containing the cryoprotectants ethylene glycol, trehalose, and dimethyl sulfoxide. During the vitrification process, embryos are first exposed to ES and then to VS. In the case of the oocytes, use BS and ES. Using this methodology, the permeating cryoprotectants can replace water in the occyte, PN through blastocyst stage embryos prior to vitrification and storage in liquid nitrogen. The Vitrification Kit comes prepackaged with one 1.5 ml vial of BS and ES, two 1.5 ml vials of VS, 4 Cryotop devices (Cryotop CL, Cryotop SC, or Cryotop US), and 2 Repro Plates.

The Thawing Kit is composed of three media used stepwise for thawing cryoprotectants from vitrified oocytes, and PN through blastocyst stage embryos. The Thawing Kit is composed of TS (Thawing Solution), DS (Dilution Solution) and WS (Wash Solution). The Thawing Kit comes pre-packaged with two 4.0 ml vials of thawing solution, one 4.0 ml vial of dilution solution, one 4.0 ml vial of washing solution, one Repro Plate, and two 35 mm dishes.

All the media in the Vitrification Kit contain Gentamicin. The media in these kits undergo aseptic filtration, while storage devices and plates are sterilized by radiation. The specifications for the Vitrification Kit and Thawing Kit are listed in Table 1 below.

#### 7. Indication for Use Statement

The Vitrification Kit is indicated for use in the preparation, vitrification and storage of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.

The Thawing Kit is indicated for use in the preparation and thawing of vitrified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.

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#### 8. Substantial Equivalence Discussion

The following table compares the Vitrification Kit to the predicate devices with respect to indications for use, principles of operation, technological characteristics, materials, and performance testing. The comparison of the devices provides more detailed information regarding the basis for the determination of substantial equivalence. As noted in the table, there are differences in indications for use and technological characteristics between the subject and predicate devices; however, the differences indications for use do not represent a new intended use, and differences in the technological characteristics do not raise any different questions of safety or effectiveness as compared to the predicate device.

| Manufacturer | Kitazato Corporation | Irvine Scientific Sales Co., Inc. |
|-------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Trade Name | Vitrification Kit and Thawing Kit | Vitrification Freeze Kit and<br>Vitrification Thaw Kit (Vit-Kit®-Thaw) |
| 510(k) Number | Not assigned | K160006 |
| Product Code | MQL, MQK | MQL |
| Regulation<br>Number | 884.6180 | 884.6180 |
| Regulation Name | Reproductive Media and Supplements | Reproductive Media and Supplements |
| Indications for Use | The Vitrification Kit is indicated for use<br>in the preparation, vitrification and<br>storage of oocytes (MII),<br>pronuclear(PN) zygotes through day 3<br>cleavage stage embryos and blastocyst<br>stage embryos.<br>The Thawing Kit is indicated for use in<br>the preparation and thawing of<br>vitrified oocytes (MII), pronuclear (PN)<br>zygotes through day 3 cleavage stage<br>embryos and blastocyst stage<br>embryos. | Vit Kit® - Freeze (Vitrification Freeze<br>Kit) is intended for use in the<br>vitrification of oocytes (MII),<br>pronuclear (PN) zygotes through day 3<br>cleavage stage embryos and blastocyst<br>stage embryos.<br>Vit Kit® - Thaw (Vitrification Thaw Kit)<br>is intended for use in the thawing of<br>oocytes (MII), pronuclear (PN) zygotes<br>through day 3 cleavage stage embryos<br>and blastocyst stage embryos. |
| Components of Kit | Vitrification Media<br>Thawing Media | Vitrification Freeze Kit<br>Vitrification Thaw Kit |
| Embryo Stage | Oocyte, PN through Blastocyst | Oocyte, PN through Blastocyst |
| Manufacturer | Kitazato Corporation | Irvine Scientific Sales Co., Inc. |
| Trade Name | Vitrification Kit and Thawing Kit | Vitrification Freeze Kit and<br>Vitrification Thaw Kit (Vit-Kit®-Thaw) |
| Principal of<br>Operation | Provides users with the ability to<br>cryopreserve supernumerary oocytes<br>or embryos created during the in vitro<br>fertilization procedure and then to re-<br>warm them for use at a future point in<br>time | Provides users with the ability to<br>cryopreserve supernumerary oocytes<br>or embryos created during the in vitro<br>fertilization procedure and then to re-<br>warm them for use at a future point in<br>time |
| Vitrification<br>Formulation | In a Medium 199 HEPES buffered<br>Medium | In a Medium 199 HEPES buffered<br>Medium |
| | Ethylene glycol | Ethylene glycol |
| | DMSO | DMSO |
| | Trehalose | Sucrose |
| | Hydroxypropyl Cellulose (HPC) | Dextran Serum Supplement (DSS) |
| | Gentamicin | Gentamicin |
| Vitrification Steps | 2 Step | 2 Step |
| Thawing<br>Formulation | In a Medium 199 HEPES buffered<br>Medium | In a Medium 199 HEPES buffered<br>Medium |
| | Hydroxypropyl Cellulose (HPC) (v/v) | Dextran Serum Supplement (DSS) (v/v) |
| | Gentamicin | Gentamicin |
| | Trehalose | Sucrose |
| Thawing Steps | 3 Step | 3 Step |
| Carton Packaging | Each solution is contained in plastic<br>vials. Vials are packed in a card board<br>outer box with partition. | Each solution is contained in plastic<br>vials. Vials are packed in a card board<br>outer box with partition. |
| Cryopreservation<br>Storage Device<br>Used With | Kitazato Corporation<br>Cryotop®CL-K112695<br>Cryotop®SC - K140072<br>Cryotop®US-K153027 | Irvine Scientific<br>HSV Straw - K092398<br>CryoTip - K041562 |
| Sterile | Solutions sterilized using aseptic<br>processing techniques through<br>filtration<br>Vial containers are sterilized via<br>radiation | Solutions sterilized using aseptic<br>processing techniques through<br>filtration<br>Vial containers are sterilized via<br>radiation |
| Manufacturer | Kitazato Corporation | Irvine Scientific Sales Co., Inc. |
| Trade Name | Vitrification Kit and Thawing Kit | Vitrification Freeze Kit and<br>Vitrification Thaw Kit (Vit-Kit®-Thaw) |
| Endotoxin | Endotoxin by LAL methodology <0.25<br>EU/mL(LAL) for Media | Endotoxin by LAL methodology<br><0.25EU/mL) |
| Mouse Embryo<br>Assay | >80% development to blastocyst at 96<br>hours | >80% one-cell 96 hours |
| Sterility Testing | Passes | Passes |
| pH Test | 7.20 - 7.60 | Not available |
| Biocompatibility | Passes | Passes |
| Storage | 2 – 8°C | 2 – 8°C |
| Shelf Life | 1 year | 1 year |

#### Table 5A - Comparison of Characteristics

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#### 9. Non-Clinical Performance Data

The subject device is identical to the Kitazato Cryotop Vitrification and Thawing Kit cleared under K160864. Design verification tests were performed on the identical device cleared under K160864. Testing included sterilization validation, packaging validation, and performance (bench) testing. The device passed all the testing. Therefore, the information provided in K160864 was leveraged in this submission to support substantial equivalence of the Vitrification Kit and Thawing Kit.

#### 10. Clinical Performance Data

The clinical information presented provides published papers that specifically identify vitrification/thawing media with HPC that are similar to or identical to the predicate device and the use of the Cryotop as the vitrification method for the cryopreservation of oocytes and blastocyst from human and mouse. A summary of the results are shown below:

- Literature 1: results of the study show comparable oocyte survival rate, implantation rate, clinical pregnancy rate, and live birth rate between a surrogate device (with similar formulation and cryoprotectants to the subject device) and vitrification media containing serum substitute supplement1
¹ A combination of hydroxypropyl cellulose as supplementation for vitrification of human oocytes: a retrospective cohort study (Coello et al, Journal of Assisted Reproduction Genetics, 2016 March; 33(3): 413-421)

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- Literature 2: results of the study show that human blastocyst survival rate following vitrification was comparable between a surrogate device (with similar formulation to the predicate device) and vitrification media containing serum substitute supplement²
- . Literature 3: results of the study show comparable oocyte survival rate to other methods of vitrification and a fertilization rate and quality blastocyst rate as comparable to fresh oocytes. 3

Birth rates following use of vitrified oocytes as compared to the vitrification methods used in the predicate device were shown to be comparable. Each of the studies reported survival rates of oocytes and embryos that are consistent with normal ART procedures using similar IVF treatments and cryopreservation techniques.

#### 11. Statement of Substantial Equivalence

The results of the performance testing described above demonstrate that the Vitrification Kit and Thawing Kit are as safe and effective as the predicate device and supports a determination of substantial equivalence.

^? Hydroxypropyl cellulose as an option for sypprotectant solutions for embryo vitrification in human assisted reproductive technologies (Mori et al, Reproductive BioMedicine Online, 2015 June;30(6):613-21)

³ Efficiency of a Closed Vitrification System with Oocytes and Blastocysts (Inoue et al, Low Temp Med, 2014; 40(3): 53-59)