Gems Vitrification Set, Gems Warming Set

K162409 · Genea Biomedx Pty, Ltd. · MQL · May 24, 2017 · Obstetrics/Gynecology

Device Facts

• Record ID: K162409
• Device Name: Gems Vitrification Set, Gems Warming Set
• Applicant: Genea Biomedx Pty, Ltd.
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: May 24, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

Gems Vitrification Set is used for the vitrification of human blastocyst stage embryos for Assisted Reproductive Technology (ART) procedures. Gems Warming Set is used for the warming of human blastocyst stage embryos that have undergone vitrification.

Device Story

Gems Vitrification Set and Gems Warming Set are media kits for cryopreservation of human blastocysts. Vitrification process: step-wise dehydration of blastocysts using cryoprotectants (ethylene glycol, DMSO, trehalose) to prevent ice crystal formation; rapid cooling in liquid nitrogen. Warming process: re-hydration of vitrified blastocysts using trehalose-based media to manage water inflow as cryoprotectants are removed. Used in clinical embryology laboratories by trained embryologists. Output is a cryopreserved or warmed embryo ready for transfer or further culture. Benefits include preservation of embryo viability for future ART procedures.

Clinical Evidence

Bench testing only. Performance validated via pH, osmolality, sterility (USP <71>), endotoxin (USP <85>), and Mouse Embryo Assay (MEA). MEA study: one-cell mouse embryos exposed to vitrification/warming sets, cultured at 37°C/5% CO2; ≥80% developed to expanded blastocyst stage at 96 hours. Shelf-life validated via real-time and accelerated studies.

Technological Characteristics

HEPES-buffered media containing salts, energy substrates, amino acids, human serum albumin, ethylene glycol, DMSO, and trehalose. Aseptic filtration (SAL 10^-3). Single-use. Shelf-life 20 weeks. Sterility per USP <71>; Endotoxin per USP <85>; MEA per internal protocol.

Indications for Use

Indicated for the vitrification and warming of human blastocyst stage embryos for patients undergoing Assisted Reproductive 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

• Cook Sydney IVF Blastocyst Vitrification Kit and Cook Sydney IVF Blastocyst Warming Kit (K143724)

Submission Summary (Full Text)

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

May 24, 2017

Genea Biomedx Pty Ltd % Roger Gray VP, Ouality Assurance and Regulatory Affairs Donawa Lifescience Consulting Srl Piazza Albania 10 Rome, 00153 Italy

Re: K162409

> Trade/Device Name: Gems Vitrification Set and Gems Warming Set Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: April 21, 2017 Received: April 24, 2017

Dear Roger Gray:

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

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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 (reporting of medical devicerelated 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 contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

Charles Viviano -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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

### Indications for Use

510(k) Number (if known) K162409

Device Name

Gems Vitrification Set and Gems Warming Set

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

Indications for Use (Describe)

Gems Vitrification Set is used for the vitrification of human blastocyst stage embryos for Assisted Reproductive Technology (ART) procedures.

Gems Warming Set is used for the warming of human blastocyst stage embryos that have undergone vitrification.

| | Over-The-Counter Use (21 CFR 801 Subpart C)<br> X Prescription Use (Part 21 CFR 801 Subpart D) | | | | |
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# 510(k) Summary

#### l. Submitter Information

| Submitter/Address: | Genea Biomedx Pty Ltd<br>Level 2, 321 Kent Street<br>Sydney<br>NSW 2000<br>Australia |
|--------------------|-------------------------------------------------------------------------------------------------------------------------------|
| Phone: | [phone] |
| Fax: | [phone] |
| Correspondent: | Mr. Roger Gray<br>VP, Quality and Regulatory<br>Donawa Lifescience Consulting Srl<br>Piazza Albania 10<br>00153 Rome<br>Italy |
| Phone: | [phone] |
| Fax: | [phone] |
| Email: | [e-mail] |
| Date Prepared: | May 22, 2017 |

## II. Date Prepared:

#### III. General Information on Devices

| Device Name: | Gems Vitrification Set and Gems Warming Set |
|----------------------|------------------------------------------------------|
| Common Name: | Vitrification and Warming Media |
| Classification Name: | Reproductive Media and Supplements (21 CFR 884.6180) |
| Product code: | MQL (Media, Reproductive) |
| Regulatory Class: | II |

#### IV. Predicate Devices

Cook Sydney IVF Blastocyst Vitrification Kit and Cook Sydney IVF Blastocyst Warming Kit (K143724)

These predicate devices have not been subject to any design-related recalls.

#### V. Indications for Use

Gems Vitrification Set is used for the vitrification of human blastocyst stage embryos for Assisted Reproductive Technology (ART) procedures.

Gems Warming Set is used for the warming of human blastocyst stage embryos that have undergone vitrification.

#### VI. Device Description

The Gems Vitrification Set and Gems Warming Set are intended for the vitrification and warming of human blastocysts as part of human ART procedures.

The Gems Vitrification Set is designed to facilitate dehydration of blastocysts before vitrification via rapid cooling in liquid nitrogen. Dehydration of the blastocysts is achieved by the step-wise use of increasing concentrations of cryoprotectants in the Gems Vitrification Set, which results in water being withdrawn from the cell. The cryoprotectants also protect the blastocysts by reducing the potential for ice crystal formation during the vitrification process.

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Image /page/4/Picture/0 description: The image contains the logo for Genea BIOMEDX. The logo consists of a green square with rounded corners and a white curved line inside, resembling a stylized "D". To the right of the square, the word "Genea" is written in gray, and below it, "BIOMEDX" is written in green.

The Gems Vitrification Set consists of three solutions (Vitsol 2, and Vitsol 3). The base formulation for Vitsol 1 and Vitsol 2 is a HEPES-buffered medium containing salts, energy substrates, amino acids, and human serum albumin. Vitsol 1 contains the cryoprotectant ethylene qlycol, while Vitsol 2 contains the cryoprotectants ethylene glycol and trehalose. Vitsol 3 consists of dimethyl sulphoxide (DMSO). The Gems Vitrification Set is not provided ready for use as Vitsol 3 must be added to the other vitrification solutions before use. Following DMSO addition to Vitsol 1 and 2, the final vitrification solutions for blastocyst vitrification procedures have the following properties:

- . Vitrification Solution 1 (Vitsol 1 + DMSO) - 8% ethylene glycol and 8% DMSO
- Vitrification Solution 2 (Vitsol 2 + DMSO) 16% ethylene glycol, 16% DMSO, and 0.57M trehalose ●

The Gems Warming Set consists of three warming solutions (Warmsol 2, and Warmsol 3), which are designed to facilitate the re-hydration (warming) of vitrified blastocysts. In the warming process, trehalose in the media manages the inflow of water into blastocysts as concentrations of DMSO and ethylene glycol are reduced during the rehydration process.

All three of the solutions in the Gems Warming Set consist of a HEPES-buffered medium containing salts, energy substrates, amino acids, and human serum albumin, with varying amounts of the cryoprotectant trehalose as described below:

- . Warmsol 1 - 1.0 M trehalose
- Warmsol 2 0.5 M trehalose ●
- Warmsol 3 - No trehalose

These media are single-use devices that are aseptically filled into sterilized bottles and have a sterility assurance level (SAL) of 10 3. The products are tested for pH, osmolality, embryotoxicity, endotoxin, and sterility before lot release.

## VII. Comparison of Intended Use and Technological Characteristics of Subject and Predicate Devices

| Parameter | Subject Device - Gems<br>Vitrification Set and<br>Gems Warming Set<br>(K162409) | Predicate Device - COOK<br>Sydney IVF Blastocyst<br>Vitrification Kit and COOK<br>Sydney IVF Blastocyst<br>Warming Kit (K143724) | Comparison |
|-----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------|
| Indication<br>for Use | Gems Vitrification Set is<br>used for the vitrification of<br>human blastocyst stage<br>embryos for Assisted<br>Reproductive Technology<br>(ART) procedures.<br>Gems Warming Set is<br>used for the warming of<br>human blastocyst stage<br>embryos that have<br>undergone vitrification. | Blastocyst Vitrification Kit is<br>intended for the vitrification<br>of human blastocysts for<br>assisted reproduction<br>technologies (ART). This kit<br>is designed for use with<br>Blastocyst Warming Kit (K-<br>SIBW-5000).<br>Blastocyst Warming Kit is<br>intended for the warming of<br>human blastocysts that have<br>undergone vitrification using<br>COOK<br>Sydney IVF Vitrification Kit<br>(K-SIBV-5000) for ART<br>procedures. | Same Intended Use -<br>vitrification and warming of<br>human blastocyst stage<br>embryos. |

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Image /page/5/Picture/0 description: The image contains the logo for Genea Biomedx. The logo consists of a green square with a white curved line inside, followed by the text "Genea" in gray and "BIOMEDX" in green. The logo is simple and modern, with a focus on the company's name and a clean design.

| Parameter | Subject Device - Gems<br>Vitrification Set and<br>Gems Warming Set<br>(K162409) | Predicate Device - COOK<br>Sydney IVF Blastocyst<br>Vitrification Kit and COOK<br>Sydney IVF Blastocyst<br>Warming Kit (K143724) | Comparison |
|-------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Formulation | HEPES buffered<br>physiologic<br>media containing ethylene<br>glycol, DMSO, trehalose,<br>and human serum<br>albumin in addition to<br>normal physiological<br>salts.<br>DMSO provided in a<br>separate vial and must be<br>added to vitrification<br>media before use. | HEPES buffered physiologic<br>media containing ethylene<br>glycol, DMSO, trehalose,<br>human Serum albumin and<br>gentamicin in addition to<br>normal physiological<br>salts.<br>DMSO provided in a<br>separate vial and must be<br>added to vitrification media<br>before use. | Different - Formulas for the<br>vitrification and Warming<br>Vitrification Solutions are similar,<br>consisting of the same<br>components with the exception<br>of gentamicin (not in subject<br>device). Some differences in<br>concentrations.<br>Differences noted above do not<br>raise different questions of<br>safety and effectiveness (S&E). |
| pH | 7.3-7.5 | 7.3-7.5 | Same |
| Osmolarity<br>(mOsm/kg) | Not applicable (N/A) for<br>vitrification solutions<br>Warmsol 1 – 1280-1320<br>Warmsol 2 – 780-820<br>Warmsol 3 - 295-305 | K-SIBV-SOL1: 285 - 295<br>K-SIBV-SOL2: N/A<br>K-SIBV-SOL3: N/A<br>K-SIBW-SOL1: 657 - 683<br>K-SIBW-SOL2: 500 - 520<br>K-SIBW-SOL3: 285 - 295 | Different: Osmolality values are<br>higher in the subject device than<br>in the predicate device due to<br>differences in cryoprotectant<br>concentrations in the subject<br>device. Differences in osmolality<br>do not raise different questions<br>of S&E. |
| MEA | 1-Cell MEA: ≥80%<br>developed to blastocysts<br>at 96h | 2-Cell MEA: ≥80%<br>blastocyst formation at 72h | Similar |
| Endotoxin | Vitsol 1-2, Warmsol 1-3<br>< 0.40 EU/mL<br>DMSO <0.05 EU/ml | < 0.40 EU/mL | Similar |
| Sterilization<br>Method | Aseptic Filtration<br>SAL 10-3 | Aseptic Filtration | Same |
| Shelf-Life | 20 weeks | 20 weeks | Same |

As noted in the table above, the devices have intended use and are technologically comparable. Differences in technological characteristics noted above do not raise different questions of safety or effectiveness.

#### VIII. Summary of Non-clinical Performance Testing

The following studies have been performed to support substantial equivalence to the predicate devices:

- pH ●
- . Osmolality
- . Aseptic Processing Validation testing that met the requirements in ISO 13408-2:2003
- Sterility testing per USP <71> .
- . Endotoxin testing per USP <85>
- . Mouse embryo assay (MEA)
- One-cell mouse embryos were exposed sequentially to subject devices in the Vitrification and Warming Sets followed by culture at 37°C in an atmosphere containing 5% CO₂. The percent of embryos developed to the expanded blastocyst stage at 96 hours were assessed in comparison with the control group.

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Image /page/6/Picture/0 description: The image shows the logo for Genea Biomedx. The logo consists of a green square with a white curved line inside, followed by the text "Genea" in gray and "BIOMEDX" in green. The logo is simple and modern, with a focus on the company's name.

- Shelf-life studies (real-time and accelerated) were conducted to ensure that the following product ● specifications are met at time zero and the end of shelf-life.
- pH 7.3-7.5 *
- * Osmolality - See technological comparison table above for specifications
- * 1-cell MEA – ≥80% developed to the blastocyst stage at 96 hours
- * Endotoxin - <0.4 EU/ml (LAL) for Vitsol 1-2, and Warmsol 1-3
- * Sterility - No microbiological growth

#### IX. Conclusions

The results of the performance testing conducted on the subject device demonstrate that it is as safe and effective as the predicate device and supports substantial equivalence.