SAGE Vitrification Kit and SAGE Vitrification Warming Kit

K170560 · CooperSurgical, Inc. · MQL · Apr 4, 2017 · Obstetrics/Gynecology

Device Facts

• Record ID: K170560
• Device Name: SAGE Vitrification Kit and SAGE Vitrification Warming Kit
• Applicant: CooperSurgical, Inc.
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Apr 4, 2017
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

SAGE Vitrification Kit: These products are intended for ultra-rapid freezing and containment of human blastocysts in assisted reproductive technology procedures. This kit is designed to be used in conjunction with the SAGE Virtification Warming Kit (ART-8031) for optimal recovery of specimens. SAGE Vitrification Warming Kit: These products are intended for the recovery of human blastocysts that have undergone ultra-rapid freezing and containment using SAGE Vitrification Kit (ART-8026) for assisted reproductive technology procedures.

Device Story

Kit consists of two sets of solutions: Vitrification Kit (Equilibration and Vitrification solutions) and Warming Kit (Sucrose and MOPS solutions). Used in ART clinics by embryologists to cryopreserve human blastocysts. Vitrification process: step-wise dehydration using cryoprotectants (DMSO, ethylene glycol, sucrose) to prevent ice crystal formation during rapid cooling in liquid nitrogen. Warming process: re-hydration using sucrose-based media to manage water inflow as cryoprotectants are removed. Solutions are aseptically filtered and supplied in single-use polypropylene vials. Modifications from predicate include transition from glass to polypropylene vials and shelf-life extension to 52 weeks. Benefits include improved specimen recovery and storage stability.

Clinical Evidence

Bench testing only. Stability testing (pH, osmolality, endotoxin, MEA, sterility) confirmed 52-week shelf-life. Transportation testing performed per ASTM D4169-08. All samples met acceptance criteria.

Technological Characteristics

MOPS-buffered media containing DMSO, ethylene glycol, sucrose, human serum albumin, gentamicin, amino acids, and salts. Supplied in 2 ml polypropylene vials. Sterilization via aseptic filtration (SAL 10^-3). Packaging sterilized via gamma irradiation. Shelf-life 52 weeks.

Indications for Use

Indicated for ultra-rapid freezing, containment, and subsequent recovery of human blastocysts in 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

• SAGE In-Vitro Fertilization, Inc. - Vitrification Kit and Vitrification Warming Kit (K073522)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or a stylized human profile, composed of three overlapping shapes.

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

April 4, 2017

CooperSurgical, Inc. % Tove Kiær Director Corporate Regulatory Affairs Origio a/s Knardrupvej 2 Måløv, 2760 Denmark

Re: K170560

Trade/Device Name: SAGE Vitrification Kit SAGE Vitrification Warming Kit Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MOL Dated: February 23, 2017 Received: March 6, 2017

Dear Tove Kjær:

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.

{1}------------------------------------------------

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 (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,

# Benjamin R. Fisher -S

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

{2}------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

# Indications for Use

510(k) Number (if known) K170560

Device Name SAGE Vitrification Kit

SAGE Vitrification Warming Kit

#### Indications for Use (Describe)

SAGE Vitrification Kit: These products are intended for ultra-rapid freezing and containment of human blastocysts in assisted reproductive technology procedures. This kit is designed to be used in conjunction with the SAGE Virtification Warming Kit (ART-8031) for optimal recovery of specimens.

SAGE Vitrification Warming Kit: These products are intended for the recovery of human blastocysts that have undergone ultra-rapid freezing and containment using SAGE Vitrification Kit (ART-8026) for assisted reproductive technology procedures.

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)

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Druq Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

Form Approved: OMB No. 0910-0120

Expiration Date: January 31, 2017

See PRA Statement below.

{3}------------------------------------------------

# 510(k) Summary

| 510(k) Number: | K170560 |
|------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submitted on behalf of | Mr. James Keller<br>Vice President, Regulatory Affairs and Quality Assurance<br>CooperSurgical, Inc<br>95 Corporate Drive<br>Trumbull, CT 06611<br>USA<br>e-mail: [e-mail]<br>Phone: +1 (203) - 601 - 5200 |
| Contact person | Ms. Tove Kjaer<br>Corporate Director Regulatory Affairs<br>Origio a/s<br>Knardrupvej 2<br>DK-2760 Måløv<br>Denmark<br>e-mail: [e-mail]<br>phone: [phone] |
| Date prepared | April 3, 2017 |
| Device identification: | |
| Trade name | SAGE Vitrification Kit<br>SAGE Vitrification Warming Kit |
| Common name | Vitrification Kit and Vitrification Warming Kit |
| Classification number | 21 CFR 884.6180, Reproductive Media and Supplements |
| Product code | MQL, Media, Reproductive |
| Regulatory class | Class II |
| Predicate device | |

SAGE In-Vitro Fertilization, Inc. - Vitrification Kit and Vitrification Warming Kit (K073522)

The predicate devices have not been subject to any design-related recall.

{4}------------------------------------------------

### Device description:

#### SAGE Vitrification Kit:

This kit includes two solutions (Equilibration Solution and Vitrification Solution). Both solutions in the kit consist of a MOPS-buffered media containing non-essential amino acids, gentamicin suffate, and human serum albumin. These solutions also contain the cryoprotectants ethylene glycol, dimethyl sulfoxide (DMSO) and sucrose as described below:

Equilibration Solution: 7.5% (v/v) each of DMSO and ethylene glycol.

Vitrification Solution: 15% (v/v) each of DMSO and ethylene glycol, and 0.6 M sucrose

#### SAGE Vitrification Warming Kit:

This kit includes three solutions (1.0 M Sucrose Warming Solution, 0.5 M Warming Solution, and MOPS Solution). All solutions in the kit consist of a MOPS-buffered media containing non-essential and essential amino acids, gentamicin sulfate, and human serum albumin. These solutions contain the cryoprotectant sucrose at the level described in their names (i.e., 1.0 M, 0.5 M, or no sucrose).

Solutions in the SAGE Vitrification Kit and SAGE Vitrification Warming Kit are aseptically-filtered and are provided to users in 2 ml polypropylene vials. The solutions in these kits are considered single-use devices.

#### Use environment:

The media are used in clinics working with assisted reproductive technology procedures

#### Device function:

The SAGE Vitrification Kit 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 concentration of cryprotectants in the SAGE Vitrification Kit, 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.

The SAGE Vitrification Warming Kit is designed to facilitate the re-hydration (warming) of blastocysts after the cells have been vitrified. In the warming process, sucrose in the media manages the inflow of water into blastocysts as concentrations of DMSO and ethylene glycol are reduced during the rehydration process.

#### Modification of existing devices:

This submission covers two modifications to the currently marketed predicate device cleared under K073522. The first modification was a change in the primary packaging from a Type I borosilicate vial with a siliconized rubber stopper and an aluminum seal to polypropylene copolymer vials. The second modification was an extension of the shelf-life from 26 weeks to 52 weeks.

#### Indication for Use

SAGE Vitrification Kit: These products are intended for ultra-rapid freezing and containment of human blastocysts in assisted reproductive technology procedures. This kit is designed to be used in conjunction with the SAGE Vitrification Warming Kit (ART-8031) for optimal recovery of specimens.

{5}------------------------------------------------

SAGE Vitrification Warming Kit: These products are intended for the recovery of human blastocysts that have undergone ultra-rapid freezing and containment using SAGE Vitrification Kit (ART-8026) for assisted reproductive technology procedures.

| Parameter | K170560 | K073522 | Comments |
|-----------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Subject Device | Predicate Device | |
| Indication for use | SAGE Vitrification Kit:<br>These products are<br>intended for ultra-rapid<br>freezing and containment<br>of human blastocysts in<br>assisted reproductive<br>technology procedures.<br>This kit is designed to be<br>used in conjunction with<br>the SAGE Vitrification<br>Warming Kit (ART-8031) for<br>optimal recovery of<br>specimens. | Vitrification Kit: These<br>products are intended for<br>ultra-rapid freezing and<br>containment of human<br>blastocysts for Assisted<br>Reproductive Technology<br>(A.R.T.) procedures. This kit<br>is designed for use with<br>Sage IVF's Vitrification<br>Warming Kit (Ref # ART-<br>8030) for optimal recovery<br>of specimens. | Similar: The indications<br>for use for the subject<br>device are similar to the<br>predicate device;<br>however, they are not<br>identical. Although<br>minor differences in<br>text exist, the<br>underlying use in<br>vitrifying and warming<br>human blastocyst stage<br>embryos is the same.<br>Therefore, the subject<br>and predicate devices<br>have the same Intended<br>Use. |
| | SAGE Vitrification Warming<br>Kit: These products are<br>intended for the recovery<br>of human blastocysts that<br>have undergone ultra-rapid<br>freezing and containment<br>using SAGE Vitrification Kit<br>(ART-8026) for assisted<br>reproductive technology<br>procedures. | Vitrification Warming Kit:<br>These products are<br>intended for the recovery<br>of human blastocysts that<br>have undergone ultra-rapid<br>freezing and containment<br>using Sage IVF's<br>Vitrification Kit (Ref # ART-<br>8025) for Assisted<br>Reproductive Technology<br>(A.R.T.) procedures. | |
| Formulation | Ethylene Glycol<br>DMSO<br>Sucrose<br>Human Serum Albumin<br>Gentamicin<br>MOPS-Buffered<br>Amino Acids<br>Normal Salts | Ethylene Glycol<br>DMSO<br>Sucrose<br>Human Serum Albumin<br>Gentamicin<br>MOPS-Buffered<br>Amino Acids<br>Normal Salts | Same |
| Cryoprotectants in<br>Vitrification Solutions | Equil. Sol. 7.5%<br>DMSO/7.5% Ethylene<br>Glycol<br>Vit. Sol.15% DMSO/15%<br>Ethylene Glycol/0.6M<br>Sucrose | Equil. Sol. 7.5%<br>DMSO/7.5% Ethylene<br>Glycol<br>Vit. Sol.15% DMSO/15%<br>Ethylene Glycol/0.6M<br>Sucrose | Same |
| Cryoprotectants in<br>Warming Solutions | 0-1.0 M Sucrose as<br>identified by solution name | 0-1.0 M Sucrose as<br>identified by solution name | Same |
| | 1.0 M Sucrose Sol.<br>0.5 M Sucrose Sol<br>MOPS Sol. (no sucrose) | 1.0 M Sucrose Sol.<br>0.5 M Sucrose Sol<br>MOPS Sol. (no sucrose) | |
| MEA | ≥80% blastocysts at 96h | ≥80% blastocysts at 96h | Same |
| Endotoxin | <0.5EU/ml | <0.5EU/ml | Same |
| Osmolality (mOsm/Kg) | Equil. Sol. 2331-2849<br>Vit. Sol. 5603-6849<br>1.0 M Sucrose 1255-1535<br>0.5M Sucrose 745-911<br>MOPS 257-273 | Equil. Sol. 2331-2849<br>Vit. Sol. 5603-6849<br>1.0 M Sucrose 1235-1535<br>0.5M Sucrose 745-911<br>MOPS 257-273 | Similar —The<br>specification for the<br>subject 1.0 M Sucrose<br>Solution is tighter than<br>that of the prior cleared<br>device. This minor<br>difference does not<br>raise different<br>questions of safety or<br>effectiveness (S&E). |
| pH | 7.2-7.4 | 7.2-7.4 | Same |
| Sterilization | Membrane filtration<br>SAL 10-3<br>USP<71> | Membrane filtration<br>SAL 10-3<br>USP<71> | Same |
| Single-Use | Single | Single | Same |
| Shelf-Life | 52 Weeks | 26 Weeks | Different - The shelf-life<br>is longer in the subject<br>device. Differences in<br>shelf-life do not raise<br>different questions of<br>S&E. |
| Device Packaging | Polypropylene vials<br>Gamma irradiated, 106 | Glass vial with a siliconized<br>rubber stopper and<br>aluminum seal.<br>Steam sterilized, 10-6 | Different - Packaging<br>has moved from steam-<br>sterilized glass vials to<br>gamma irradiated<br>polypropylene vials.<br>Differences in vial<br>materials/sterilization<br>methods do not raise<br>different questions of<br>S&E. |

# Comparison of Intended Use and Technological Characteristics

{6}------------------------------------------------

{7}------------------------------------------------

As noted in the table above, the devices have the same intended use and are technologically comparable. Differences in technological characteristics noted included a minor difference in the osmolality specification for one media, and differences in shelf-life length and device packaging. As noted in the table, these differences do not raise different questions of safety or effectiveness.

#### Sterilization

Solutions in these kits are aseptically filtered, and have a Sterility Assurance Level of 10 °. Validation of the media sterilization process was not re-assed in the current submission as the aseptic filtration process is the same as that provided in the predicate submission (K073522).

#### Stability and Shelf-life:

Real-time shelf-life testing was conducted to demonstrate a 52-week shelf-life for the SAGE Vitrification Kit and SAGE Vitrification Warming Kit.

Stability testing included assessments of pH, osmolality, endotoxin, MEA, and sterility. All devices tested met the acceptance criteria described in the comparison table above.

#### Transportation testing:

Transportation testing on the SAGE Vitrification Kit and SAGE Vitrification Warming Kit was conducted in accordance with ASTM D4169-08, Standard Practice for Performance Testing of Shipping Containers and Systems. Samples tested did not show any signs of negative effects from simulated handling/transportation and met vial leakage acceptance specifications.

#### Conclusion:

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.