The Cryotop®CL 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

CryotopCL 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.

The CryotopCL device is composed of PET plastic shaft with a fine tip and a straw cap. The fine tip has 5 rounded depressed areas for loading embryos. The CryotopCL 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 protective straw cap has a weighted end to allow proper alignment in the storage container. The CryotopCL device is provided sterile and is for single use only. The device is also provided with a pushing straw to aid in loading the sample holding component of the device into the "straw" enclosure system.

The CryotopCL 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 CryotopCL is validated by sterilization validation to maintain the sterility of the device through anticipated storage and handling.

AI/ML Overview

Acceptance Criteria and Device Performance Study for Kitazato's Cryotop®CL

This document describes the acceptance criteria and the study used to demonstrate that Kitazato's Cryotop®CL device met these criteria, based on the provided 510(k) summary (K112695).

1. Table of Acceptance Criteria and Reported Device Performance

Test Type	Acceptance Criteria	Reported Device Performance
Cooling Rate Testing	3,000 °C/min (for the device to function as intended)	3,000 °C/min Passed
Warming Rate Testing	40,000 °C/min (for the device to function as intended)	40,000 °C/min Passed
Dimensional Testing	Outer diameter, length, width of shaft, and spacing of embryo holding locations according to specifications	Passed specifications
Mechanical Tensile Testing	Withstand 5N	Withstood 5N
Endotoxin Testing	≤0.5 EU/device	≤0.5 EU/device
Sterility Testing	No microbial growth, SAL 10^-6^	No microbial growth, SAL 10^-6^
Mouse Embryo Assay (MEA)	≥80% of 1-cell control embryos develop at 96 hours	≥80% of 1-cell control embryos developed at 96 hours
Overall Performance	All specifications met acceptance criteria	All specifications met acceptance criteria

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

The provided document does not explicitly state the specific sample sizes used for each individual test (e.g., number of devices tested for cooling rate, endotoxin, etc.). However, it indicates:

Test Set Description: The "Non-Clinical Testing" section lists various tests performed on the CryotopCL device.
Sample Size: Not explicitly stated as a single number for all tests. For the Mouse Embryo Assay, the acceptance criteria relates to the percentage of 1-cell control embryos that develop, implying a sample of embryos within a test.
Data Provenance: Retrospective, as the testing was performed during the development and validation phase of the device prior to submission. The origin of the data is from KITAZATO BioPharma Co., Ltd. in Japan, as they are the submission sponsor and manufacturer.

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

The document does not mention the use of external experts or a ground truth panel to establish the "ground truth" for the non-clinical performance tests. The tests performed are objective, quantitative measurements (e.g., temperature rates, physical dimensions, endotoxin levels, sterility checks) or standardized biological assays (Mouse Embryo Assay). These types of tests typically rely on established protocols and measurement standards rather than expert consensus on a "ground truth" definition for individual cases.

4. Adjudication Method for the Test Set

Not applicable. As noted above, the non-clinical tests are objective and quantitative; therefore, an adjudication method for conflicting expert opinions is not relevant. The results are compared directly against predefined numerical or qualitative acceptance criteria.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was done. The submission explicitly states: "There was no clinical testing required to support the medical device as the indications for use is equivalent to the predicate devices." Therefore, no study involving human readers (with or without AI assistance) was conducted to assess improvement.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Not applicable. The Cryotop®CL is a physical medical device (cryopreservation storage device) and not an AI algorithm. Therefore, no standalone algorithm performance study was conducted.

7. Type of Ground Truth Used

For the non-clinical tests, the "ground truth" is defined by:

Predefined physical specifications: For dimensional and mechanical tests.
Established scientific thresholds: For cooling/warming rates, endotoxin levels, and sterility (e.g., no microbial growth, SAL 10^-6^).
Standardized biological assay outcomes: For the Mouse Embryo Assay, the ground truth is the viability/development of 1-cell control embryos at 96 hours as observed in the assay.

8. Sample Size for the Training Set

Not applicable. This is a physical medical device, not an AI/machine learning system that requires a training set.

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

Not applicable, as there is no training set for this device.

Summary

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pg. 1 of 4

510(k) Summary

DEC 1 2 2012

for

Kitazato's Cryotop®CL, K112695

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

Submission Correspondent 2.

Emergo Group 611 West 5th Street, Third Floor 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

7 December 2012

4. Device Name

Cryotop®CL Trade/Proprietary Name: Cryotop Closed Common/Usual Name: Classification Name: Assisted Reproduction Labware Classification Regulation: 884.6160 Obstetrics/Gynecology Classification Panel: Product Code: MQK Device Class: ll

5. Predicate Devices

Cryo Bio System, HSV Straw, K092398

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Pg. 2 of 4
K112695

Device Description 6.

CryotopCL 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.

7. Indication for Use

The Cryotop®CL 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.

8. Technological Characteristics and Substantial Equivalence

The following table compares Kitizato's CryotopCL to the predicate device with respect to intended use, technological characteristics, and principles of operation.

Manufacturer	KITAZATO BioPharma Co., Ltd.	Cryo Bio System
Trade Name	Cryotop®CL	HSV Straw
510(k) Number	K112695	K092398
Product Code	MQK	MQK
Regulation Number	884.6160	884.6160
Regulation Name	Assisted Reproduction Labware	Assisted Reproduction Labware
Indications for Use:	The CryotopCL is acryopreservation storage devicethat is intended for use invitrification procedures to containand maintain human 4-8 cell andblastocyst stage embryos.	The HSV Straw is acryopreservation storage devicethat is intended for use invitrification procedures to containand maintain human 4-8 cell andblastocyst stage embryos.
Overall Design	The device consists of a threepiece assembly comprised of themain part containing the fine tip,the protective "straw," andpushing tool to assist in the properplacement of the main part. Thestraw is designed to be sealed.	The device consists of 3 parts: aresin straw, a capillary tube with apre-formed gutter attached to acolored handling rod, and a plasticpushing tool to assist in theproper placement of the capillarytube. The straw is designed to be

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Pg. 3 of 4
K112695

Manufacturer	KITAZATO BioPharma Co., Ltd.	Cryo Bio System
Trade Name	Cryotop®CL	HSV Straw
	The straw is weighted to allowproper alignment in the storagecontainer. The CryotopCL deviceis packaged in a single peel offblister pack that is terminallysterilized; 10 (ten) units are placedin a secondary paper pouch forstorage purposes.	sealed. The HSV Straw is packagedin a peel off blister pack.
Method of Action	Vitrification Method	Vitrification Method
Sterile	Radiation	Radiation
Cooling Rate	3,000°C/min	2,900°C/min
Rewarming Rate	40,000°C/min	25,000°C/min
Material Composition	PET, Polypropylene	Medical Grade Styrene-ButadieneCopolymer
Contact withWarming Medium	The tip (film) and the shaft ofCryotopCL are taken out fromstraw. Directly immerse the tip(film) into warming medium.	The curved spatula, containing thecryopreserved embryo, isimmersed in warming mediumwhere thawing and dilution in thewarming medium occursimultaneously.
Performance Testingof Device	Passed	Passed
Mouse Embryo TestPassed	≥80% of 1-cell control embryos	≥80% of 1-cell control embryos
Endotoxin Testing	≤0.5 EU/device	≤0.5 EU/device
Sterility ValidationPassed	No microbial growth, SAL 10-6	No microbial growth, SAL 10-6

9. Non-Clinical Testing

The CryotopCL device has undergone cooling/warming rate testing, mechanical testing, The Cryolopce device has andergone obsing, wouse embryo assay testing, and endotoxin testing, dimensional testing, stermsy cosing, ""
Results support that all the specifications have met the acceptance criteria for the device.

Cooling Rate Testing: Cooling rate of 3,000 °C/min passed �
Cooling Rate Testing: Warming rate of 40,000 °C/min passed �
warming nate Testing: Passes outer diameter, length, width of shaft, and spacing of .
the embryo holding locations according to specifications
Mechanical Tensile Testing: Tensile strength to withstand 5N .
Mechanied Terror: Endotoxin values conform to the value ≤0.5 EU/device ●
Sterility Testing: No microbial growth from sterility testing .
Stenity Yesting 10 % of 1-cell control embryos develop at 96 hours .

The CryotopCL device passed all testing and supports the claims of substantial equivalence.

The CryotopCL device complies with the applicable voluntary standards for sterilization. The The Clyotopee de nee complise with national and international standards.
device passed all the testing in accordance with national and international standards.

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Pg. 4 of 4
R112695

10. Clinical Testing

There was no clinical testing required to support the medical device as the indications for use is equivalent to the predicate devices. 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. Conclusion

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.

It has been shown in this 510(k) submission that the difference between the CryotopCL device and the predicate devices do not raise any new types of questions regarding its safety and effectiveness. Kitazato's Cryotop®CL, as designed and manufactured, is determined to be substantially equivalent to the referenced predicate devices.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird with three stylized wing segments.

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

December 12, 2012

KITAZATO BioPharma Co., Ltd. % Mr. Richard Vincins, CQA, CBA, RAC (US, EU) Vice President, Quality Assurance Emergo Group 611 West 5th Street, Third Floor AUSTIN TX 78701

Re: K112695

Trade/Device Name: Cryotop®CL Regulation Number: 21 CFR§ 884.6160 Regulation Name: Assisted reproduction labware Regulatory Class: II Product Code: MQK Dated: November 21, 2012 Received: November 23, 2012

Dear Mr. 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 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.

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Page 2 - Mr. Richard 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/CDRH0ffices/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,

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

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Section 4 - Indications for Use Statement

510(k) Number (if known): K112695

Device Name: Cryotop®CL

Indications for Use:

The Cryotop®CL 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.

(Part 21 CFR 801 Subpart D) Prescription Use × 1 AND/OR Over-The-Counter Use ______________________________ (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Benjamin R. Fisher -S 2012.12.12 11/110:49 -05'00'

(Division Sign-Off) ision of Reproductive, Gastro-Renal, and logical Devices (k) Number

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.