Vitavitro Vitrification Kit, Vitavitro Warming Kit, and Vitavitro Straw Set

K180073 · Shenzhen Vitavitro Bio-Tech Co., Ltd. · MQL · Aug 29, 2018 · Obstetrics/Gynecology

Device Facts

• Record ID: K180073
• Device Name: Vitavitro Vitrification Kit, Vitavitro Warming Kit, and Vitavitro Straw Set
• Applicant: Shenzhen Vitavitro Bio-Tech Co., Ltd.
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Aug 29, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

VitaVitro Vitrification Kit is intended for the vitrification of human blastocysts for assisted reproduction technologies (ART). This kit is designed for use with VitaVitro Warming Kit. VitaVitro Warming Kit is intended for the warming of human blastocysts that have undergone vitrification using VitaVitro Vitrification Kit for ART procedures. VitaVitro Straw Set is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human blastocyst stage embryos.

Device Story

System comprises vitrification media, warming media, and cryopreservation storage straw set. Media kits contain cryoprotectants (ethylene glycol, DMSO, sucrose) to replace water in blastocysts during vitrification and rehydrate during warming. Straw set consists of copolyester straw and protective container; straw tip draws 1 µl media/blastocyst sample; container pre-cooled in liquid nitrogen; straw inserted into container and heat-sealed to create closed system. Used in clinical ART laboratories by embryologists. Benefits include cryopreservation of blastocysts for future use. Output is vitrified/warmed embryo ready for clinical transfer.

Clinical Evidence

Bench testing only. Performance validated via pH, osmolality, endotoxin (<0.25 EU/mL for media, <0.5 EU/device for straw), and Mouse Embryo Assay (MEA). MEA demonstrated ≥80% development to expanded blastocyst stage at 72h. Straw set validated for cooling (5,127°C/min) and warming (17,899°C/min) rates, sealed device durability in liquid nitrogen, and package integrity per ASTM standards.

Technological Characteristics

Media: Medium 199 base, ethylene glycol, DMSO, sucrose, HSA. Storage device: Copolyester. Closed system. Sterilization: Aseptic filtration (media), Ethylene Oxide (straws). Shelf-life: 6 months. Standards: USP<85> (endotoxin), USP<71> (sterility), ISO 13408-1/2 (aseptic processing), ASTM D4169-16 (distribution), ASTM F1929:2012/F88:2009 (package integrity).

Indications for Use

Indicated for vitrification, storage, and warming of human blastocyst stage embryos in assisted reproduction technology (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

• Cryotop® Vitrification Kit and Cryotop® Thawing Kit (K160864)

Submission Summary (Full Text)

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August 29, 2018

Shenzhen Vitavitro Bio-tech Co., Ltd % Field Fu Consultant Shenzhen Joyantech Consulting Co., Ltd NO. 55 Shizhou middle road, Nanshan District Shenzhen. Guangdong 518000 CHINA

Re: K180073

> Trade/Device Name: VitaVitro Vitrification Kit, VitaVitro Warming Kit, and VitaVitro Straw Set Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL, MQK Dated: July 26, 2018 Received: August 2, 2018

Dear Field Fu:

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 mav, 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 avare 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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

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,

# Sharon M. Andrews -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) K180073

Device Name

VitaVitro Vitrification Kit,VitaVitro Warming Kit, and VitaVitro Straw Set

Indications for Use (Describe)

VitaVitro Vitrification Kit is intended for the vitrification of human blastocysts for assisted reproduction technologies (ART). This kit is designed for use with VitaVitro Warming Kit.

VitaVitto Warming Kit is intended for the warming of human blastocysts that have undergone vitrification using VitaVitro Vitrification Kit for ART procedures.

Vita Vitro Straw Set is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human blastocyst stage embryos.

| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------|--|
|-------------------------------------------------|--|

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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# 510(k) Summary K180073

#### 1. Contact Details

| 1.1 Applicant information | |
|---------------------------|--|
|---------------------------|--|

| Applicant Name | Shenzhen VitaVitro Bio-tech Co., Ltd |
|----------------------------|--------------------------------------------------------------------------------------------|
| Address | R601, Building B, Hai Ke Xing Tech Park, Baoshan Road<br>No.16, Shenzhen, Guangdong, China |
| Phone No. | [phone] |
| Fax No. | [phone] |
| Contact person | Jenny Lin |
| Contact person's<br>e-mail | [e-mail] |
| Date Prepared | August 25, 2018 |

#### 1.2 Submission Correspondent

| Correspondent Name | Shenzhen Joyantech Consulting Co., Ltd |
|--------------------|--------------------------------------------------------------------------------------------------------------|
| Address | Room 1122, International Mayors Communication Centre, No. 55 Shizhou middle road, Nanshan District, Shenzhen |
| Phone No. | [phone] |
| Contact person | Field Fu; Christy Young; Jessie You; |
| Contact e-mail | [e-mail]; [e-mail];[e-mail] |

#### 2. Device information

| Trade name | VitaVitro Vitrification Kit, VitaVitro Warming Kit, and VitaVitro<br>Straw Set |
|-------------------|--------------------------------------------------------------------------------|
| Common name | Vitrification Cryopreservation Media and storage devices |
| Regulation Name | Reproductive media and supplements |
| Regulation Number | 884.6180 |
| Product Codes | MQL (Media, Reproductive) and MQK (Labware, Assisted<br>Reproduction) |
| Device Class | II |

### 3. Legally Marketed Predicate Device

| Trade Name | Cryotop® Vitrification Kit and Cryotop® Thawing Kit |
|---------------|-----------------------------------------------------|
| 510(k) Number | K160864 |
| Manufacturer | KITAZATO BioPharma Co., Ltd. |

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

### 4. Device Description

VitaVitro Vitrification and Warming Kits, and the VitaVitro Straw Set are used for vitrification, storage, and warming of blastocysts as part of human assisted reproduction technology (ART) procedures.

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The VitaVitro Vitrification Kit includes three media components, Human Holding Medium (HHM), Human Vitrification Solution 1 (HV1) and Human Vitrification Solution 2 (HV2). All three media have the same base formulation, but HV1 and HV2 contain the cryoprotectants ethylene glycol and dimethyl sulfoxide in increasing concentrations. HV2 also includes sucrose as a non-permeating cryoprotectant. During the vitrification process, blastocysts are first equilibrated in HHM, and then exposed sequentially to HV1 and HV2. Using this methodology, the permeating cryoprotectants replace water in the blastocyst prior to vitrification and storage in liquid nitrogen. The VitaVitro Vitrification Kit includes single 1.0 ml vials of HHM, HV1, and HV2.

The VitaVitro Warming Kit includes three media used stepwise for warming and removing cryoprotectants from vitrified blastocysts. The VitaVitro Warming Kit includes Human Warming Solution 1 (HW1), Human Warming Solution 2 (HW2) and HHM. These media products are the same with the exception that HW1 and HW2 also include sucrose in decreasing concentrations to aid in the rehydration of the blastocysts. The VitaVitro Warming Kit includes two 1.5 ml vials of HW1, one 1.0 ml vial of HW2, and one 1.8 ml vial of HHM.

The VitaVitro Straw Set consists of two components, a straw that holds the blastocysts, and a container that is used to protect the straw. Both components are made from copolyester. The closed end of the container also includes a weight to aid in maintaining the orientation of the device in liquid nitrogen and prevent floating. During use, the container is pre-cooled by placing the closed end in liquid nitrogen with the open end extending above the level of the liquid nitrogen. Straw loading is done by placing the narrow tip of the straw in a 1 µl drop of vitrification media, which draws the media and blastocysts into the storage device. The straw component is then inserted into the pre-cooled container component to effect vitrification. The container component is then sealed to prevent contact between the samples and liquid nitrogen.

All of the products are provided sterile with a six-month shelf-life. The media in the vitrification and warming kits undergo aseptic filtration, while the storage devices are ethylene oxide sterilized.

#### 5. Indications for Use

VitaVitro Vitrification Kit is intended for the vitrification of human blastocysts for assisted reproduction technologies (ART). This kit is designed for use with VitaVitro Warming Kit.

VitaVitro Warming Kit is intended for the warming of human blastocysts that have undergone vitrification using VitaVitro Vitrification Kit for ART procedures.

VitaVitro Straw Set is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human blastocyst stage embryos.

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## 6. Substantial Equivalence Comparison

The following table compares the Vitrification Kit, VitaVitro Warming Kit, and VitaVitro Straw Set to the predicate device:

| | Subject Device | Predicate Device | Comparison |
|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | K180073 – VitaVitro | K160864 – Kitazato | |
| | Vitrification Kit, | Cryotop | |
| | VitaVitro Warming Kit, | Vitrification Kit and | |
| | and VitaVitro Straw Set | Cryotop Thawing | |
| | | Kit | |
| Indications<br>for Use | VitaVitro Vitrification Kit<br>is intended for the<br>vitrification of human<br>blastocysts for assisted<br>reproduction<br>technologies (ART). This<br>kit is designed for use<br>with VitaVitro Warming<br>Kit.<br><br>VitaVitro Warming Kit is<br>intended for the warming<br>of human blastocysts<br>that have undergone<br>vitrification using<br>VitaVitro Vitrification Kit<br>for ART procedures.<br><br>VitaVitro Straw Set is a<br>cryopreservation storage<br>device that is intended<br>for use in vitrification<br>procedures to contain<br>and maintain human<br>blastocyst stage<br>embryos. | The Cryotop®<br>Vitrification Kit –<br>Vitrification is<br>indicated<br>for use in the<br>preparation,<br>vitrification<br>and storage of<br>pronuclear (PN)<br>zygotes<br>through day 3<br>cleavage<br>stage embryos and<br>blastocyst stage<br>embryos.<br><br>The Cryotop®<br>Thawing<br>Kit – Thawing is<br>indicated for use in<br>the<br>preparation and<br>thawing of vitrified<br>pronuclear (PN)<br>zygotes<br>through day 3<br>cleavage<br>stage embryos and<br>blastocyst stage<br>embryos. | Different: The subject and<br>predicate devices indications<br>are not identical. All<br>components of the subject<br>device are only for vitrification,<br>storage and warming of<br>blastocyst stage embryos,<br>while the predicate can be<br>used with pronuclear to<br>blastocyst stage embryos. The<br>subject device also includes a<br>standalone indication for the<br>VitaVitro Straw Set, which is<br>sold separately from the media<br>kits, which is different than the<br>predicate where storage<br>devices are included within the<br>vitrification kit. These<br>differences do not impact the<br>overall intended uses of these<br>devices, which are the same<br>(vitrification, storage, and<br>thawing of embryos). |
| Components | Vitrification Media<br>Thawing Media | Vitrification Media<br>Thawing Media | Different: Predicate device<br>includes plates as a |
| | Cryopreservation<br>storage device | Cryotop<br>Repro Plate<br>35 mm dish | convenience to users that<br>would typically be obtained<br>separately. The storage device<br>for the subject device is<br>provided separately as<br>compared to the predicate.<br>These differences do not raise<br>different questions of safety<br>and effectiveness (S&E). |
| | <b>Media Components</b> | | |
| Vitrification<br>Formulation | Medium 199, Ethylene<br>Glycol (7.5 – 16%),<br>DMSO (7.5 – 16%),<br>Sucrose (0.68 M), HSA | Medium 199,<br>Ethylene Glycol,<br>DMSO, Trehalose,<br>Hydroxypropyl<br>Cellulose (specific<br>concentrations in<br>predicate media not<br>known) | Different: The predicate and<br>subject device formulas<br>include many similar<br>components. However, the<br>predicate uses trehalose<br>instead of sucrose and<br>hydroxypropyl cellulose<br>instead of serum. However, the<br>use of a different sugar/serum<br>replacer do not raise different<br>questions of S&E. In<br>addition, the concentrations of<br>specific components in the<br>predicate media are not<br>known; however, differences<br>would not raise different<br>questions of S&E. |
| Thawing<br>Formulation | Medium 199, Sucrose<br>(0.5 – 1 M), HSA | Medium 199,<br>Trehalose,<br>Hydroxypropyl<br>Cellulose | Different: The predicate and<br>subject device formulas<br>include many similar<br>components. However, the<br>predicate utilizes trehalose<br>instead of sucrose and<br>hydroxypropyl cellulose<br>instead of serum (see rationale<br>above). In addition, the<br>concentrations of specific<br>components in the predicate<br>media are not known;<br>however, differences would not<br>raise different questions of<br>S&E. |
| Endotoxin | < 0.25 EU/mL | Same | Same |
| MEA | 2-Cell MEA: > 80% | 1-Cell MEA: > 80% | Different: Testing using a 1-cell |
| | blastocysts 72h | blastocysts 96 h | or 2-cell method does not raise<br>different S&E questions. |
| pH | 7.2 - 7.6 | Same | Same |
| Osmolarity | HHM: 295-315<br>HV1: N/A<br>HV2: N/A<br>HW1: 600-850 (diluted<br>1:1)<br>HW2: 850-1000 | ES: 2,300 - 2,800<br>VS: 4,900 - 6,000<br>TS: 1,600 - 2,000<br>DS: 830 - 1020<br>WS: 240 - 300 | Different: The osmolality<br>specifications are different<br>between the subject and<br>predicate devices.<br>Differences in osmolality do<br>not raise different questions of<br>S&E. |
| Sterilization<br>method | Aseptic filtration | Same | Same |
| | Storage Devices | | |
| Material<br>composition | Copolyester | Cryotop US,<br>Cryotop SC, or<br>Cryotop CL provided<br>in kits<br><br>Cryotop devices<br>composed of PET,<br>ABS, and<br>Polypropylene | Different: The materials in the<br>subject and predicate device<br>are different. These<br>differences do not raise<br>different questions of S&E. |
| Sealing<br>mechanism | Heat sealed | Cryotop US - The<br>shaft handle<br>contains a taper and<br>stop. When inserted<br>into the straw, a<br>hermetically sealed<br>closed system is<br>formed.<br><br>Cryotop SC and CL-<br>the sample holding<br>stick is heat sealed<br>within an outer<br>straw. | Different: The subject device<br>has a comparable<br>design/closure system to that<br>used in the Cryotop SC and CL<br>devices, but is different than<br>the Cryotop US. This<br>difference does not raise<br>different S&E questions. |
| Cooling Rate | 5,127 °C/min | 3000°C/min for all<br>versions | Different: The subject device<br>has a higher cooling rate than<br>the predicate. A higher<br>cooling rate does not raise<br>different questions of S&E. |
| Warming | 17,899 °C/min | 44000°C/min for all | Different: The subject device |
| rate | | versions | has a lower warming rate than<br>the predicate. A lower<br>warming rate does not raise<br>different questions of S&E.<br>Note: the warming rate for the<br>subject device is in line with<br>other cleared devices of this<br>type. |
| Open/closed<br>system | Closed | Closed | Same |
| Sterilization<br>method | EO | Radiation | Different: The subject and<br>predicate device use different<br>sterilization methods that are<br>both common for medical<br>devices. This difference does<br>not raise different questions of<br>S&E. |
| MEA | 2-Cell MEA: ≥ 80%<br>blastocysts 72 h | 1-Cell MEA: ≥ 80%<br>blastocysts 96 h | Different: Testing using a 1-cell<br>or 2-cell method does not raise<br>different S&E questions. |
| Endotoxin | < 0.5 EU/device | Same | Same |

#### Table 1 – Comparison of Characteristics

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As shown in the table above, the intended uses of the subject and predicate devices are the same. In addition, the table shows many similarities between the subject and predicate devices; however, there are also differences (e.g., formulation, specifications, etc.). The differences noted between the subject and predicate device do not raise different questions of safety and effectiveness for the reasons stated in the table.

### 7. Non-clinical Performance Testing

### VitaVitro Vitrification Kit and VitaVitro Warming Kit

- pH: 7.2-7.6 for all solutions .
- Osmolality: see Table 1 for acceptance specifications .
- Endotoxin (USP<85>): <0.25 EU/mL .
- Mouse Embryo Assay (MEA): .
- Two-cell mouse embryos were exposed sequentially to subject devices in the Vitrification and Warming Kits followed by culture at 37°C in an atmosphere containing 5% CO2. The percent of embryos developed to the expanded blastocyst stage at 72 hours were assessed in comparison with the control group. The acceptance specification was ≥80% development to blastocyst at 72h.
- Aseptic processing and validation testing that met the requirements of ISO 13408-1:2008 . and ISO 13408-2:2003.
- . Sterility Testing (USP<71>)
- Shelf-life testing to ensure that product specifications for pH, osmolality, MEA, endotoxin, .

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and sterility, were met over the six-month shelf-life period.

#### VitaVitro Straw Set

- . Cooling Rate Testing: Cooling rate of 5,127℃/min
- Warming Rate Testing: Warming rate of 17,899°C/min .
- . Endotoxin (USP<85>): <0.5 EU/device
- . Mouse Embryo Assay (MEA):

Two-cell mouse embryos were exposed to test article extracts (media incubated with the test article for 30 min at 37°C) followed by culture at 37°C in an atmosphere containing 5% CO2. The percent of embryos developed to the expanded blastocyst stage at 72 hours were assessed in comparison with the control group. The acceptance specification was ≥80% development to blastocyst at 72h.

- Sealed Device Durability: No burst/breakage after 30 second immersion in liquid nitrogen .
- Simulated distribution testing per ASTM D4169-16 .
- Package integrity testing per ASTM F1929:2012 (dye penetration) and ASTM F88:2009 ● (seal strength) to support sterile barrier maintenance over the shelf-life of the device.
- . Shelf-life testing to ensure that product specifications for endotoxin, MEA, cooling/warming rate, and sealed device durability were met over the six-month shelf-life period.

### 8. Conclusion

The results of the performance testing described above demonstrates that the VitaVitro Vitrification Kit, VitaVitro Warming Kit, and VitaVitro Straw Set are as safe and effective as the predicate device and supports a determination of substantial equivalence.