RapidVit™ Oocyte, RapidWarm™ Oocyte

K183486 · Vitrolife Sweden AB · MQL · Jul 26, 2019 · Obstetrics/Gynecology

Device Facts

• Record ID: K183486
• Device Name: RapidVit™ Oocyte, RapidWarm™ Oocyte
• Applicant: Vitrolife Sweden AB
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Jul 26, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

RapidVit™ Oocyte: Media for vitrification of human oocytes (MII). RapidWarm™ Oocyte: Media for warming of vitrified human oocytes (MII).

Device Story

RapidVit™ Oocyte and RapidWarm™ Oocyte are media kits for cryopreservation of human MII oocytes; used in clinical embryology laboratories by trained personnel. RapidVit™ involves sequential exposure of oocytes to three solutions (Vitri 1, 2, 3) containing cryoprotectants (ethylene glycol, propanediol) and sucrose to dehydrate and protect cells during vitrification. RapidWarm™ involves sequential exposure to four solutions (Warm 1-4) with decreasing sucrose concentrations to rehydrate oocytes. Media are aseptically filled in 10 ml bottles. Output is the successful vitrification and subsequent warming of oocytes for use in IVF; clinical benefit is the preservation of oocyte viability for future reproductive procedures.

Clinical Evidence

Clinical study of 593 oocytes from 64 donors. Results: 94% oocyte survival rate (555/593), 78% fertilization rate (434/555), 24% Day 5 blastulation rate (102/434), 35% Day 5/6 utilization rate (153/434), and 50% clinical pregnancy rate (27/54 recipients). Bench testing included pH, osmolality, sterility (USP <71>), bacterial endotoxins (USP <85>), and Mouse Embryo Assay (MEA) with >80% blastocyst development success.

Technological Characteristics

Media kits containing amino acids, MOPS, Human Serum Albumin, ethylene glycol, propanediol, sucrose, gentamicin, and hyaluronan. Aseptically filtered; 10 ml plastic bottles. Shelf-life 25 weeks; stable 2 weeks post-opening. Testing per USP <791> (pH), USP <785> (osmolality), and ISO 11137-1:2006/11137-2:2013 (aseptic filling).

Indications for Use

Indicated for the vitrification and warming of human MII oocytes for use in assisted reproduction 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® Freeze (Vitrification Freeze Kit), Vit Kit® Thaw (Vitrification Thaw Kit) (K160006)

Submission Summary (Full Text)

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July 26, 2019

Vitrolife Sweden AB Nina Arvidsson Regulatory Affairs Manager Gustaf Werners gata 2 SE 421 32 Vastra Frolunda SWEDEN

Re: K183486

> Trade/Device Name: RapidVit™ Oocyte, RapidWarm™ Oocyte Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: II Product Code: MOL Dated: June 24, 2019 Received: June 26, 2019

Dear Nina Arvidsson:

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. Although this letter refers to your product as a device, please be aware 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

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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 adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Sharon M. Andrews Assistant Division Director DHT3B: Division of Reproductive, Gynecology and Urology Devices OHT3: Office of Gastrorenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K183486

Device Name

RapidVit "M Oocyte, RapidWarm TM Oocyte

#### Indications for Use (Describe)

RapidVit™ Oocyte: Media for vitrification of human oocytes (MII).

RapidWarm The Oocyte: Media for warming of vitrified human oocytes (MII).

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

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Image /page/3/Picture/1 description: The image shows the word "Vitrolife" in blue font. The font is a serif font, and the letters are all capitalized except for the "i" in "Vitrolife". To the right of the word "Vitrolife" is a blue swoosh that is also in blue. The swoosh is a stylized wave.

### 510(k) Summary (K183486)

### 1. Submitter Information

| Submitted by: | Vitrolife Sweden AB<br>Gustaf Werners gata 2<br>SE - 421 32 Västra Frölunda<br>Sweden |
|--------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Nina Arvidsson<br>Vitrolife Sweden AB<br>Gustaf Werners gata 2<br>SE - 421 32 Västra Frölunda<br>Sweden<br>Phone: [phone]<br>Fax: [phone]<br>Email: [e-mail] |
| 2. Date Prepared | July 24, 2019 |
| 3. Device Identification | |
| Trade Name: | RapidVitTM Oocyte, RapidWarmTM Oocyte |
| Common Name: | Oocyte Vitrification/Warming Kit |
| Regulatory Class: | Class II |
| Regulation Number: | 21 CFR 884.6180 |
| Regulation Name: | Reproductive Media and Supplements |
| Product Code: | MQL (Media, Reproductive) |

- Vit Kit® Freeze (Vitrification Freeze Kit), Vit Kit® Thaw (Vitrification Thaw Kit) - (K160006) manufactured by Irvine Scientific. The predicate device has not been subject to a design related recall.
### 5. Device Description

Two sets of media are covered by this 510(k), the RapidVit™ Oocyte for vitrification of oocytes and the RapidWarm™ Oocyte for warming of vitrified oocytes. RapidVit™ Oocyte contains three medium solutions to be used sequentially during oocyte vitrification. RapidWarm™ Oocyte includes four medium solutions to be used sequentially during oocyte warming. The table below outlines the components contained in RapidVit™ Oocyte and RapidWarm™ Oocyte.

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| Component | Formulation characteristics | Utilization |
|------------------|----------------------------------------------------------------------------|------------------------------|
| Vitri 1TM Oocyte | Contains no cryoprotectants | First step of vitrification |
| Vitri 2TM Oocyte | Contains cryoprotectants (ethylene glycol [8%] and propanediol [8%]) | Second step of vitrification |
| Vitri 3TM Oocyte | Contains (ethylene glycol [16%], propanediol [16%], and sucrose [0.442 M]) | Third step of vitrification |
| Warm 1TM Oocyte | Contains sucrose (1 M) | First step of warming |
| Warm 2TM Oocyte | Contains sucrose (0.5 M) | Second step of warming |
| Warm 3TM Oocyte | Contains sucrose (0.25 M) | Third step of warming |
| Warm 4TM Oocyte | Contains no sucrose | Fourth step of warming |

All media are aseptically filtered and filled in 10 ml plastic bottles and have a 25-week shelf-life under recommended storage conditions. They are stable for 2 weeks after opening of the packaging bottle, if stored under recommended conditions.

## 6. Indications for Use

RapidVit™ Oocyte: Media for vitrification of human oocytes (MII). RapidWarm™ Oocyte: Media for warming of vitrified human oocytes (MII).

# 7. Substantial Equivalence Discussion

| Device | K183486 (subject device) | K160006 (predicate device) |
|-------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for<br>Use | RapidVitTM Oocyte - Media for<br>vitrification of human oocytes<br>(MII). | Vit Kit® - Freeze (Vitrification Freeze<br>Kit) is intended for use in the vitrification<br>of oocytes (MII), pronuclear (PN) zygotes<br>through day 3 cleavage stage embryos<br>and blastocyst stage embryos. |
| | RapidWarmTM Oocyte - Media<br>for warming of vitrified human<br>oocytes (MII). | Vit Kit® - Thaw (Vitrification Thaw Kit)<br>is intended for use in the thawing of<br>vitrified oocytes (MII), pronuclear (PN)<br>zygotes through day 3 cleavage stage<br>embryos and blastocyst stage embryos. |
| pH | 7.2-7.4 | Vitrification media – 7.05-7.54<br>Warming media – 7.05-7.44 |
| Osmolality<br>(mOsm/kg) | Vitri 1TM Oocyte: 272-288<br>Vitri 2TM Oocyte: 3045-3355<br>Vitri 3TM Oocyte: 6530-7370<br>Warm 1TM Oocyte: 1450-1610<br>Warm 2TM Oocyte: 800-900 | ES Freeze: 1055-1445<br>VS Freeze: 1100-1588<br>TS Thaw: 1732-1912<br>DS Thaw: 857-910<br>WS Thaw: 268-292 |

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| | Warm 3TM Oocyte: 560-600<br>Warm 4™ Oocyte: 272-288 | |
|---------------------------------------------|---------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------|
| Key components<br>in vitrification<br>media | Amino acids<br>MOPS<br>Human Serum Albumin<br>Ethylene glycol<br>Sucrose<br>Gentamicin<br>Propanediol<br>Hyaluronan | Medium 199<br>Dextran serum supplement<br>Amino acids<br>Ethylene glycol<br>Sucrose<br>Gentamicin<br>DMSO |
| Key components<br>in warming<br>media | Amino acids<br>Human Serum Albumin<br>Sucrose<br>Gentamicin<br>Hyaluronan | Medium 199<br>Dextran serum supplement<br>Amino acids<br>Sucrose<br>Gentamicin |

Both subject and predicate devices are indicated for vitrification of oocytes and warming of vitrified human MII oocytes, while the predicate device is also indicated for vitrification of embryos (PN-blastocyst stages). Although the subject device has a more limited indication, the intended use (i.e., vitrification and warming of oocytes for use in assisted reproduction procedures) is the same.

The subject and predicate devices are different in technological characteristics, including pH. osmolality, and formulation. These differences do not raise different questions of safety and effectiveness, and are common in assisted reproduction technology media devices.

## 8. Summary of Non-Clinical Performance Testing

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

- pH testing per USP <791> ●
- . Osmolality testing per USP <785>
- Aseptic filling validation study per ISO 11137-1:2006 and ISO 11137-2:2013 ●
- Bacterial endotoxins testing per USP <85> (acceptance criterion: < 0.5 EU/ml) .
- Sterility testing per USP <71> (acceptance criterion: no microbial growth) ●
- Mouse Embryo Assay (MEA) using established protocol: .

One-cell mouse embryos were exposed sequentially to each vitrification solution and each warming solution using exposure conditions identical to the maximum exposure durations stated in the Instructions for Use. The embryos were then cultured at 37°C in an atmosphere containing 5% CO2. The percentage of embryos developed to the expanded

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blastocyst stage within 96 hours were assessed in comparison with the control group. The acceptance specification is ">80% of embryos expand to the blastocyst stage by 96h."

- Shelf-life testing was conducted to ensure that the following product specifications are . met at time zero and end of shelf-life (25 weeks): pH, osmolality, sterility, 1-cell MEA, and endotoxin.
- Stability testing was conducted to ensure that the following product specifications are met . at two weeks after opening of packaging bottles: pH, osmolality, sterility, 1-cell MEA, and endotoxin.

# 9. Summary of Clinical Performance Testing

A clinical study was conducted to evaluate clinical performance of the subject device using 593 oocytes from 64 donors. The study showed the oocyte survival rate of 94% after vitrification (555/593), fertilization rate of 78% (434/555), Day 5 blastulation rate of 24% (102/434), Day 5/6 utilization rate of 35% (153/434), and clinical pregnancy (confirmed by fetal heartbeat) rate of 50% (27/54 recipients).

## 10. Conclusion

The subject and predicate devices have the same intended use and comparable technological characteristics. The differences in technological characteristics between the subject and predicate devices do not raise different questions of safety and effectiveness. The performance data demonstrate that the subject device is substantially equivalent to the predicate device.