Sequential Culture Media (Fertilization Medium [without HSA/rHA, with HSA, with rHA], Cleavage Medium [without HSA/rHA, with HSA, with rHA], Blastocyst Medium [without HSA/rHA, with HSA, with rHA])

K200249 · Kitazato Corporation · MQL · Oct 23, 2020 · Obstetrics/Gynecology

Device Facts

• Record ID: K200249
• Device Name: Sequential Culture Media (Fertilization Medium [without HSA/rHA, with HSA, with rHA], Cleavage Medium [without HSA/rHA, with HSA, with rHA], Blastocyst Medium [without HSA/rHA, with HSA, with rHA])
• Applicant: Kitazato Corporation
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Oct 23, 2020
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

Sequential Culture Media consists of Fertilization Medium, and Blastocyst Medium that are intended to be used sequentially from fertilization to the blastocyst stage of development. The intended uses of the Fertilization Medium, Cleavage Medium, and Blastocyst Medium are as follows: Fertilization medium is intended for use during in vitro fertilization (IVF) and intracytoplasmic sperm insertion (ICSI) procedures and culture to the two pronuclei (zygote) stage of development. Cleavage Medium is intended for culture of embryos from the two pronuclei (zygote) stage of development. Cleavage Medium is not intended for transferring embryos to the uterine cavity Blastocyst Medium is intended for culture from the 8-cell stage to the blastocyst stage of development. Blastocyst Medium is not intended for transferring embryos to the uterine cavity

Device Story

Sequential Culture Media supports in vitro fertilization (IVF) and intracytoplasmic sperm insertion (ICSI) procedures. The device consists of three distinct media variants—Fertilization, Cleavage, and Blastocyst—used sequentially to support embryo development from the zygote stage to the blastocyst stage. The media provide necessary salts, energy substrates, buffers, antioxidants, nutrients, amino acids, and antibiotics (gentamicin) to maintain embryo viability. The device is used in clinical laboratory settings by embryologists. The media are provided sterile-filtered in PETG vials or bottles. By providing a controlled environment for embryo development, the device facilitates successful assisted reproduction technology procedures. The output is the cultured embryo, which is then assessed by the clinician for potential transfer. The device is not intended for the transfer of embryos to the uterine cavity.

Clinical Evidence

Bench testing only. Performance validated via Mouse Embryo Assay (MEA) (≥80% development to expanded blastocyst at 96 hours), pH (7.2-7.6), osmolality (270-295 mOsm/L), endotoxin levels (≤0.25 EU/mL), and sterility (no growth). Stability testing conducted over 4 months. Container integrity validated per USP <671> and transportation testing per ASTM D4169.

Technological Characteristics

Reproductive culture media containing salts, energy substrates, buffers, antioxidants, nutrients, amino acids, and gentamicin. Provided in PETG containers (sterile-filtered, gamma-irradiated). pH 7.2-7.6; osmolality 270-295 mOsm/L. Storage at 2-8°C. Shelf life 4 months. Single-use.

Indications for Use

Indicated for use in patients undergoing in vitro fertilization (IVF) and intracytoplasmic sperm insertion (ICSI) procedures for the sequential culture of embryos from fertilization through the blastocyst stage of development.

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

• Sydney IVF Fertilization Medium, Cleavage Medium, Blastocyst Medium (K153290)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. Underneath the square are the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.

October 23, 2020

Kitazato Corporation % Audrey Swearingen Regulatory Affairs Manager Emergo Global Consulting, LLC 2500 Bee Cave Road, Building 1, Suite 300 Austin, TX 78746

Re: K200249

> Trade/Device Name: Sequential Culture Media (Fertilization Medium [without HSA/rHA, with HSA, with rHA], Cleavage Medium [without HSA/rHA, with HSA, with rHA], and Blastocyst Medium [without HSA/rHA, with HSA, with rHA]) Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: September 22, 2020 Received: September 24, 2020

Dear Audrey Swearingen:

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/cdrl/cfdocs/cfpmn/pmn.cfm_identifies_combination product submissions. The general controls provisions of the Actinclude 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.

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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 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-devices/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 (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.

Monica D. Garcia, Ph.D. Assistant Director DHT3B: Division of Reproductive. Gynecology and Urology Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known) K200249

#### Device Name

Sequential Culture Media (Fertilization Medium [with HSA, with rHA], Cleavage Medium [without HSA/rHA, with HSA, with rHA], and Blastocyst Medium [without HSA/rHA, with HSA, with rHA])

#### Indications for Use (Describe)

Sequential Culture Media consists of Fertilization Medium, and Blastocyst Medium that are intended to be used sequentially from fertilization to the blastocyst stage of development. The intended uses of the Fertilization Medium, Cleavage Medium, and Blastocyst Medium are as follows:

Fertilization medium is intended for use during in vitro fertilization (IVF) and intracytoplasmic sperm insertion (ICSI) procedures and culture to the two pronuclei (zygote) stage of development.

Cleavage Medium is intended for culture of embryos from the two pronuclei (zygote) stage of development. Cleavage Medium is not intended for transferring embryos to the uterine cavity

Blastocyst Medium is intended for culture from the 8-cell stage to the blastocyst stage of development. Blastocyst Medium is not intended for transferring embryos to the uterine cavity

| Type of Use (Select one or both, as applicable) | |
|------------------------------------------------------------------------------------------------|---------------------------------------------|
| <span style="text-decoration: overline;">X</span> Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |

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# 510(k) Summary

# K200249 - Sequential Culture Media (Fertilization Medium [without HSA/rHA, with HSA, with rHA], Cleavage Medium [without HSA/rHA, with HSA, with rHA], Blastocyst Medium [without HSA/rHA, with HSA, with rHA])

#### 1. Submitter Information

| Applicant: | Kitazato Corporation |
|------------|---------------------------------------|
| Contact: | Mr. Futoshi Inoue |
| | President and Representative Director |
| Address: | 81 Nakajima, Fuji-shi |
| | Shizuoka 416-0907 |
| | Japan |
| Phone: | [phone] |

#### 2. Correspondent Information

| Contact: | Audrey Swearingen<br>Regulatory Affairs Manager / Senior Consultant |
|----------|--------------------------------------------------------------------------------------------------|
| Address: | Emergo Global Consulting, LLC<br>2500 Bee Cave Road<br>Building 1, Suite 300<br>Austin, TX 78746 |
| Phone: | [phone] |
| Email: | [e-mail] |

#### 3. Date Prepared

October 23, 2020

#### 4. Device Identification

| Device Name: | Sequential Culture Media (Fertilization Medium [without HSA/rHA, with<br>HSA, with rHA], Cleavage Medium [without HSA/rHA, with HSA, with<br>rHA], Blastocyst Medium [without HSA/rHA, with HSA, with rHA]) |
|--------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | Reproductive Culture Media |
| Regulation Number: | 21 CFR 884.6180 |
| Regulation Name: | Reproductive media and supplements |
| Product Code: | MQL (Media, Reproductive) |

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Class:

Class II

### 5. Predicate Device

| Device Name: | Sydney IVF Fertilization Medium, Cleavage Medium, Blastocyst Medium |
|----------------|---------------------------------------------------------------------|
| 510(k) Number: | K153290 |
| Manufacturer: | Cook Medical, Inc. |

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

#### 6. Device Description

Sequential Culture Media are intended for use sequentially from fertilization to late embryonic stages during assisted reproduction technology procedures for insemination and embryo culture.

The Sequential Culture Media is provided in three variants: Fertilization Medium, Cleavage Medium, and Blastocyst Medium. Each variant is provided with or without protein (human serum albumin (HSA) or recombinant HSA (rHA)). All variants contain gentamicin, an antibiotic agent that suppresses bacterial growth. Each Sequential Culture Media solution is offered in three volumes (10mL, 50mL and 100mL).

The following models are provided:

| Model No. | Description |
|-----------|--------------------------------------------------------------|
| SK01-10 | Sequential Culture Media Fertilization Medium 10mL |
| SK01-50 | Sequential Culture Media Fertilization Medium 50mL |
| SK01-100 | Sequential Culture Media Fertilization Medium 100mL |
| SK01S-10 | Sequential Culture Media Fertilization Medium with HSA 10mL |
| SK01S-50 | Sequential Culture Media Fertilization Medium with HSA 50mL |
| SK01S-100 | Sequential Culture Media Fertilization Medium with HSA 100mL |
| SK01C-10 | Sequential Culture Media Fertilization Medium with rHA 10mL |
| SK01C-50 | Sequential Culture Media Fertilization Medium with rHA 50mL |
| SK01C-100 | Sequential Culture Media Fertilization Medium with rHA 100mL |
| SK02-10 | Sequential Culture Media Cleavage Medium 10mL |
| SK02-50 | Sequential Culture Media Cleavage Medium 50mL |
| SK02-100 | Sequential Culture Media Cleavage Medium 100mL |
| SK02S-10 | Sequential Culture Media Cleavage Medium with HSA 10mL |
| SK02S-50 | Sequential Culture Media Cleavage Medium with HSA 50mL |
| SK02S-100 | Sequential Culture Media Cleavage Medium with HSA 100mL |
| SK02C-10 | Sequential Culture Media Cleavage Medium with rHA 10mL |
| SK02C-50 | Sequential Culture Media Cleavage Medium with rHA 50mL |
| SK02C-100 | Sequential Culture Media Cleavage Medium with rHA 100mL |
| SK03-10 | Sequential Culture Media Blastocyst Medium 10mL |
| SK03-50 | Sequential Culture Media Blastocyst Medium 50mL |
| SK03-100 | Sequential Culture Media Blastocyst Medium 100mL |

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| SK03S-10 | Sequential Culture Media Blastocyst Medium with HSA 10mL |
|-----------|-----------------------------------------------------------|
| SK03S-50 | Sequential Culture Media Blastocyst Medium with HSA 50mL |
| SK03S-100 | Sequential Culture Media Blastocyst Medium with HSA 100mL |
| SK03C-10 | Sequential Culture Media Blastocyst Medium with rHA 10mL |
| SK03C-50 | Sequential Culture Media Blastocyst Medium with rHA 50mL |
| SK03C-100 | Sequential Culture Media Blastocyst Medium with rHA 100mL |

The Sequential Culture Media solution is a colorless, clear fluid, provided sterile-filtered into a container pre-sterilized by gamma irradiation. The primary container of Sequential Culture Media 10mL is a sterile non-pyrogenic PETG vial, and the primary container of the Sequential Culture Media 50mL and 100mL is a square, non-pyrogenic PETG bottle. The containers are manufactured and provided sterile (with a SAL of 10° ) by ThermoFisher Scientific, Inc. After sterilefilling, the top of the vial and bottle are sealed with tamper-evident shrink-wrap.

The complete device specifications are listed in Table 1 below.

#### 7. Indication for Use Statement

Sequential Culture Media consists of Fertilization Medium, Cleavage Medium, and Blastocyst Medium that are intended to be used sequentially from fertilization to the blastocyst stage of development. The intended uses of the Fertilization Medium, Cleavage Medium, and Blastocyst Medium are as follows:

Fertilization medium is intended for use during in vitro fertilization (IVF) and intracytoplasmic sperm insertion (ICSI) procedures and culture to the two pronuclei (zygote) stage of development.

Cleavage Medium is intended for culture of embryos from the two pronuclei (zygote) stage to the 8cell stage of development. Cleavage Medium is not intended for transferring embryos to the uterine cavity.

Blastocyst Medium is intended for culture from the 8-cell stage to the blastocyst stage of development. Blastocyst Medium is not intended for transferring embryos to the uterine cavity.

#### 8. Substantial Equivalence Discussion

The following table compares the intended use and technological features of the subject and predicate device:

| | K200249:<br>Kitazato Sequential Culture<br>Media | K153290:<br>Cook Sydney IVF Media | |
|----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------|
| Device<br>Attribute | | | Comparison |
| Manufacturer | Kitazato | Cook Medical, Inc. | Different |
| Product Code | MQL | MQL | Same |
| Indications for Use | Sequential Culture Media<br>consists of Fertilization | Sydney IVF Fertilization<br>Medium is intended for use | Different |
| | Medium, Cleavage Medium,<br>and Blastocyst Medium that<br>are intended to be used<br>sequentially from<br>fertilization to the blastocyst<br>stage of development. The<br>intended uses of the<br>Fertilization Medium,<br>Cleavage Medium, and<br>Blastocyst Medium are as<br>follows:<br>Fertilization medium is<br>intended for use during in<br>vitro fertilization (IVF) and<br>intracytoplasmic sperm<br>insertion (ICSI) procedures<br>and culture to the two<br>pronuclei (zygote) stage of<br>development.<br>Cleavage Medium is<br>intended for culture of<br>embryos from the two<br>pronuclei (zygote) stage to<br>the 8-cell stage of<br>development. Cleavage<br>Medium is not intended for<br>transferring embryos to the<br>uterine cavity.<br>Blastocyst Medium is<br>intended for culture from<br>the 8-cell stage to the<br>blastocyst stage of<br>development. Blastocyst<br>Medium is not intended for<br>transferring embryos to the<br>uterine cavity. | during in vitro procedures<br>for insemination and<br>incubation of oocytes.<br>Sydney IVF Cleavage<br>Medium is intended for use<br>during in vitro fertilization<br>procedures for culture and<br>transfer of cleavage stage<br>embryos.<br>Sydney IVF Blastocyst<br>Medium is intended for use<br>during in vitro fertilization<br>procedures for extended<br>culture and transfer of<br>embryos. | |
| Rx/OTC | Rx | Rx | Same |
| Volumes | 10, 50, 100 mL | 20, 50, 100 mL | Different |
| Ingredients | Salts, Energy substrates,<br>Buffer, anti-oxidant, nutrient<br>supplements, Amino acids,<br>Antibiotic, protein | Salts, Energy substrates,<br>Buffer, anti-oxidant,<br>nutrient supplements,<br>Amino acids, Antibiotic,<br>protein | Different |
| pH | 7.2-7.6 | 7.5-7.8 | Different |
| Osmolality | 270-290 mOsm/L | - Fertilization Medium:<br>285-295mOsm/kg<br>- Cleavage Medium:<br>285-295mOsm/kg<br>- Blastocyst Medium:<br>280-290mOsm/kg | Different |
| Endotoxin | $\le$ 0.25 EU/mL | < 0.4 EU/mL | Different |
| MEA | $\ge$ 80% of one cell mouse<br>embryos developed to<br>expanded blastocyst at 96<br>hours | $\ge$ 80% expanded blastocyst<br>at 72 hours | Different |
| Sterilization method | Sterile-filtered | Sterile-filtered | Same |
| Sterility | No growth | No growth | Same |
| Single-Use | Yes | Yes | Same |
| Storage Condition | 2 – 8 $^{\circ}$ C | 2 – 8 $^{\circ}$ C | Same |
| Shelf Life | 4 months | 20 weeks | Different |

#### Table 1 - Comparison of Characteristics

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The subject and predicate device have similar indications for use statements and have the same intended use - to support fertilization and embryo development in assisted reproductive technology procedures. The subject and predicate device have different technological characteristics, including differences in formulation, pH, osmolality, endotoxin, storage conditions, MEA, and shelf-life. These differences do not raise different questions of safety and effectiveness as compared to the predicate device.

#### 9. Summary of Non-Clinical Performance Testing

To demonstrate safety and effectiveness of Sequential Culture Media and to show substantial equivalence to the predicate device, Kitazato Corporation completed the following non-clinical tests. Results confirm that the design inputs and performance specifications for the Sequential Culture Media are met.

The Sequential Culture Media passed all testing in accordance with internal requirements, national standards, and international standards shown below:

- . Performance Testing:
- Appearance: Clear, particulate-free o
- pH, per USP <791>: 7.2 7.6 O
- O Osmolarity, using freezing depression method: 270-295 mOsm/L
- Endotoxin, per USP <85>: ≤ 0.25 EU/mL O
- O MEA: ≥ 80% of 1-cell mouse embryos developed to expanded blastocyst at 96 hours
- Sterility, per USP <71>: No microbial growth O

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- . Stability testing: real-time aged samples at baseline (Time 0) and 4 months for the performance specifications above
- . Sterile filtration and aseptic fill validation, per ISO 13408-1:2008/A1:2013 and ISO 13408-2:2018
- . Container Seal testing, per USP <671>: ≤ 5.0% permeability and ≤ 1 sample exceeding 2.50% over the 14 days
- . Transportation Testing per ASTM D4169 – Package integrity and device performance maintained

#### 10. Conclusions

The results of the performance testing described above demonstrate that the Sequential Culture Media are as safe and effective as the predicate device and supports a determination of substantial equivalence.