The Cryotop®SC is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell and blastocyst stage embryos.

Device Description

CryotopSC is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell and blastocyst stage embryos. Extracting embryos from the body can be costly and burdensome process for the patient to go through multiple extraction procedures. As part of the vitrification procedure, the cells to be stored are loaded on the tip of the CryotopSC device for subsequent storage.

The CryotopSC device is composed of an ABS handle shaft with a PET fine tip and a straw enclosure. The fine tip has a flat film area for loading embryos. The CryotopSC device has a "straw" enclosure system for when the unit is placed in the liquid nitrogen. The straw cap is designed to be heat sealed by the user. The straw cap has a weight at the distal end to place the straw cap and the shaft inside of the cap in a correct position in the liquid nitrogen. The CryotopSC device is provided sterile and is for single use only. The CryotopSC device has been designed to maintain the integrity of the human embryos through the freezing and thawing process.

The Aluminum Block is required for use with the CryotopSC device for the vitrification and thawing process and is sold separately. The Aluminum Block is to be used with the CryotopSC device to prevent liquid nitrogen from entering the straw and to assist in stabilizing the manipulation of the straw.

The CryotopSC device conforms to product quality test specifications of our company: appearance, dimension, durability, tensile strength, colorfastness, endotoxin and Mouse Embryo Assay. The sterilization dose of CryotopSC is validated by sterilization to maintain the sterility of the device through anticipated storage and handling.

AI/ML Overview

The provided text describes the 510(k) submission for the Cryotop®SC cryopreservation storage device. It focuses on demonstrating substantial equivalence to a predicate device through non-clinical performance testing rather than a study proving the device directly meets acceptance criteria in a clinical context with human users.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Cooling Rate	3,000 °C/min (Passed)
Warming Rate	44,000 °C/min (Passed)
Dimensional Specifications	Passes outer diameter and length according to specifications
Mechanical Tensile Strength	Withstand 5N (Passed)
Endotoxin Level	≤0.5 EU/device (Conformed)
Sterility	No microbial growth (Passed)
Mouse Embryo Assay (MEA) Development Rate	≥80% of 1-cell control embryos develop at 96 hours (Passed)

2. Sample Size Used for the Test Set and Data Provenance

The document states that the performance testing, Mouse Embryo Assay (MEA), and sterility tests are “all performed on samples from routine manufactured lots”. It does not specify a particular sample size for each test, nor does it provide details on data provenance such as country of origin. The data is retrospective in the sense that it's performed on manufactured lots, but the context is pre-market submission.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

This information is not applicable/not provided in the document. The Cryotop®SC is a physical device for cryopreservation, and its performance is evaluated through material and biological tests, not by human expert assessment of a test set in the way a diagnostic AI would be. The "ground truth" for these tests is based on established scientific and manufacturing standards (e.g., specific cooling/warming rates, mechanical strength thresholds, endotoxin limits, embryo development rates).

4. Adjudication Method for the Test Set

This information is not applicable/not provided. Adjudication methods like 2+1 or 3+1 typically apply to studies where multiple human readers interpret data, and their findings need to be reconciled to establish a ground truth. Since this device is evaluated through objective physical and biological tests, such an adjudication method is not relevant.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This information is not applicable/not provided. The Cryotop®SC is a physical medical device (cryopreservation storage device) and not an Artificial Intelligence (AI) or software as a medical device (SaMD) that would typically be evaluated in an MRMC study related to human reader performance or AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

This information is not applicable/not provided. As explained above, the Cryotop®SC is a physical device, not an algorithm, so a standalone algorithm performance study is not relevant.

7. The Type of Ground Truth Used

The ground truth used for the performance testing includes:

Quantitative Thresholds/Specifications: For cooling rate, warming rate, dimensional compliance, mechanical tensile strength, and endotoxin levels. These are objective numerical values that the device must meet.
Absence of Growth/Contamination: For sterility testing (absence of microbial growth).
Biological Viability Percentage: For the Mouse Embryo Assay (MEA), typically defined as a certain percentage of embryos reaching a specific developmental stage (≥80% of 1-cell control embryos develop at 96 hours). This is a biological "ground truth" established through a standard assay.

8. The Sample Size for the Training Set

This information is not applicable/not provided. The Cryotop®SC is a physical device, and its development does not involve a "training set" in the context of machine learning or AI. Its design and manufacturing are based on engineering principles and material science.

9. How the Ground Truth for the Training Set was Established

This information is not applicable/not provided for the same reasons as point 8.

Summary

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510(k) Summary

for

CRYOTOP®SC

1. Submission Sponsor

KITAZATO BioPharma Co., Ltd. 81 Nakajima, Fuji Shizuoka 416-0907 JAPAN Phone: +(81) 545-66-2202 Fax: +(81) 545-60-5772 Contact: Futoshi INOUE, President

2. Submission Correspondent

Emergo Group 816 Congress Avenue, Suite 1400 Austin, TX 78701 Cell Phone: (508) 838.9139 Office Phone: (512) 327.9997 Fax: (512) 327.9998 Contact: Richard VINCINS, Vice President, QA Email: project.management@emergogroup.com

3. Date Prepared

1 April 2014

4. Device Identification

Cryotop®SC Trade/Proprietary Name: Cryopreservation storage device Common/Usual Name: Assisted Reproduction Labware Classification Name: 884.6160 Classification Regulation: MQK Product Code: Device Class: Class II Classification Panel: Obstetrics/Gynecology

5. Legally Marketed Predicate Device(s)

Cryo Bio System, HSV Straw, K092398

..............................................................................................................................................................................

APR 0 3 2014

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6. Device Description

7. Indication for Use Statement

The Cryotop®SC is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell and blastocyst stage embryos.

Substantial Equivalence Discussion 8.

The following table compares the CryotopSC to the predicate device with respect to intended use, technological characteristics and principles of operation, providing more detailed information regarding the basis for the determination of substantial equivalence.

ManufacturerTrade Name	KITAZATO BioPharma Co., Ltd.Cryotop®SC	Cryo Bio SystemHSV Straw
510(k) Number	Not assigned	K092398
Product Code	MQK	MQK
Regulation Number	884.6160	884.6160
Regulation Name	Assisted Reproduction Labware	Assisted Reproduction Labware
Indications for Use:	The CryotopSC is acryopreservation storage devicethat is intended for use in	The HSV Straw is a cryopreservationstorage device that is intended foruse in vitrification procedures to

	Table 5A - Comparison of Characteristics

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Manufacturer	KITAZATO BioPharma Co., Ltd.	Cryo Bio System
Trade Name	Cryotop ® SC	HSV Straw
	vitrification procedures to containand maintain human 4-8 cell andblastocyst stage embryos.	contain and maintain human 4-8 celland blastocyst stage embryos.
Overall Design	The CryotopSC is designed tocontain, freeze and maintainembryos. The device consists of atwo piece assembly comprised ofthe main part containing the finetip film area and the "straw." Thestraw is designed to be sealed. Thestraw is weighted to allow properalignment in the storage container.The CryotopSC device is packagedin a single barrier sterilizationpouch.	The HSV Straw is designed tocontain, vitrify and maintainembryos.The device consists of 3 parts: a resinstraw, a capillary tube with a pre-formed gutter attached to a coloredhandling rod, and a blue plasticinsertion device.The straw is designed to be sealed.The HSV Straw is packaged in a peeloff blister pack.
Method of Action	Vitrification Method	Vitrification Method
Sterile	Radiation	Radiation
Cooling Rate	3,000°C/min	2,900°C/min
Rewarming Rate	44,000°C/min	25,000°C/min
Material Composition	PET, ABS, Polypropylene	Medical Grade Styrene-ButadieneCopolymer, Ionomeric resin
Contact with WarmingMedium	The tip (film) and the shaft ofCryotopSC are taken out from thestraw. Directly immerse the tip(film) into thawing solution.	The curved spatula, containing thecryopreserved embryo, is immersedin thawing solution where thawingand dilution in the thawing solutionoccur simultaneously.
Performance Testing ofDevice	Passed	Passed
Mouse Embryo TestPassed	Yes	Yes
Sterility ValidationPassed	Yes	Yes

Non-Clinical Performance Data 9.

The CryotopSC device has been evaluated for the cooling/warming rate, mechanically tested, sterility tested, and mouse embryo assay supporting that all the specifications have met the acceptance criteria for the device. The following testing has been performed to support substantial equivalence:

Performance Testing

Cooling Rate Testing: Cooling rate of 3,000 °C/min passed .
Warming Rate Testing: Warming rate of 44,000 °C/min passed .
Dimensional Testing: Passes outer diameter and length according to specifications .
Mechanical Tensile Testing: Tensile strength to withstand 5N .
Endotoxin Testing: Endotoxin values conform to the value ≤0.5 EU/device .
Sterility Testing: No microbial growth from sterility testing .
Mouse Embryo Assay: ≥80% of 1-cell control embryos develop at 96 hours .

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Note: The performance testing, Mouse Embryo Assay (MEA), and sterility test are all performed on samples from routine manufactured lots; a Certificate of Analysis is provided with each lot of CryotopSC device.

The CryotopSC device passed all testing and supports the claims of substantial equivalence. The CryotopSC meets all the requirements for overall design, sterilization, functional, and mouse embryo assay testing confirms that the output meets the design inputs and specifications. The CryotopSC passed all testing stated above as shown by the acceptable results obtained.

The CryotopSC device complies with the applicable voluntary standards for sterilization. The device passed all the testing in accordance with national and international standards.

10. Clinical Performance Data

There was no clinical testing required to support the medical device as the indications for use is equivalent to the predicate device. The substantial equivalence of the device is supported by the non-clinical testing. The validation testing of sterility testing and mouse embryo testing was found to acceptable and supports the claims of substantial equivalence.

11. Statement of Substantial Equivalence

By definition, a device is substantially equivalent to a predicate device when the device has the same intended use and the same technological characteristics as the previously cleared predicate device. Or the device has the same intended use and different technological characteristics that can be demonstrated that the device is substantially equivalent to the predicate device, and that the new device does not raise different questions regarding its safety and effectiveness as compared to the predicate device.

KITAZATO BioPharma's Cryotop®SC, as designed and manufactured, is determined to be substantially equivalent to the referenced predicate devices.

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Public Health Service

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

April 3, 2014

KITAZATO BioPharma Co., Ltd. % Richard A. VINCINS, CQA, CBA, RAC (US, EU) Vice President, QA Emergo Group 816 Congress Avenue, Suite 1400 Austin, TX 78701

K140072 Re:

Trade/Device Name: Cryotop®SC Regulation Number: 21 CFR§ 884.6160 Regulation Name: Assisted reproduction labware Regulatory Class: II Product Code: MQK Dated: January 10, 2014 Received: January 13, 2014

Dear Richard A. VINCINS,

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 I loast of 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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Page 2 - Richard A. VINCINS, CQA, CBA, RAC (US, EU)

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 device-related 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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Image /page/5/Picture/6 description: The image shows the name "Benjamin Fisher -S" in a bold, sans-serif font. The letters "FDA" are stylized and overlaid on top of the name. The letters "FDA" are outlined with a thick border and have a decorative pattern inside.

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

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

510(k) Number (if known)

K140072

Device Name Cryotop@SC

Indications for Use (Describe)

The Cryotop®SC is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell and 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)

PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON A SEPARATE PAGE IF NEEDED.

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Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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Regulation Number and Section

§ 884.6160 Assisted reproduction labware.

(a)
Identification. Assisted reproduction labware consists of laboratory equipment or supplies intended to prepare, store, manipulate, or transfer human gametes or embryos for in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), or other assisted reproduction procedures. These include syringes, IVF tissue culture dishes, IVF tissue culture plates, pipette tips, dishes, plates, and other vessels that come into physical contact with gametes, embryos or tissue culture media.(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, and clinical testing). The device, when it is a dish or plate intended for general assisted reproduction technology procedures, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.