The Cryotop®US 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

CryotopUS 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. As part of the vitrification procedure, the cells to be stored are loaded on the tip of the CryotopUS device for subsequent storage.

The CryotopUS device is composed of an acrylonitrile butadiene styrene (ABS) handle shaft with a polyethylene terephthalate (PET) film tip and a polypropylene straw enclosure. The fine tip has a flat film area for loading embryos. The CryotopUS device has a "straw" enclosure system for when the unit is placed in the liquid nitrogen. The handle shaft is designed with a "stop" for inserting the film tip/shaft handle into the straw enclosure. A hermetic seal is created via a tapered shaft handle with a stop location integrated into the handle is placed into the straw enclosure this creates a closed system keeping the film tip isolated from the liquid nitrogen. The straw enclosure system has a weight at the distal end to place the straw and the shaft inside in a correct position in the liquid nitrogen. The CryotopUS device is provided sterile and is for single use only. The CryotopUS device has been designed to maintain the integrity of the human embryos through the freezing and thawing process.

AI/ML Overview

The provided document describes the performance testing of the Cryotop®US cryopreservation storage device. Here's a breakdown of the acceptance criteria and the study details:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criterion	Reported Device Performance
Cooling Rate	3,000 °C/min (Passed)
Warming Rate	44,000 °C/min (Passed)
Dimensional	Passes outer diameter and length according to specifications
Durability	No burst or liquid nitrogen inside the straw after 30 second immersion
Mechanical Tensile	Tensile strength to withstand 5N
Endotoxin	≤0.5 EU/device (Conforms to the value)
Sterility	No microbial growth from sterility testing
Mouse Embryo Assay (MEA)	≥80% of 1-cell control embryos develop at 96 hours
Shelf Life	Test performed, outcome implies satisfactory (Passed)
Package Integrity	Test performed, outcome implies satisfactory (Passed)

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

The document does not explicitly state the numerical sample size used for each "test set." It mentions that the performance testing, Mouse Embryo Assay (MEA), and sterility tests are "all performed on samples from routine manufactured lots." This suggests that the testing is ongoing quality control rather than a single, fixed sample size for a specific study.

The data provenance is not explicitly stated in terms of country of origin or whether it's retrospective or prospective. Given that it's for a new device attempting to prove substantial equivalence, the testing would generally be prospective, conducted by the manufacturer (KITAZATO BioPharma Co., Ltd. from JAPAN).

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

This information is not provided in the document. The tests performed are objective physical and biological assays (e.g., cooling rate, biochemical levels, embryonic development), and their results are typically assessed against pre-defined numerical thresholds or standards rather than expert consensus on a "ground truth" as might be seen for diagnostic imaging interpretation.

4. Adjudication Method for the Test Set

This information is not applicable/not provided as the acceptance criteria are based on objective measurements and established standards, not on subjective interpretations by multiple experts.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The document describes non-clinical performance data comparing the device to a predicate device based on technical characteristics and objective performance tests, not human reader performance with or without AI assistance.

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

No, a standalone (algorithm only) performance study was not done. This device is a physical medical device (cryopreservation storage device), not an AI algorithm.

7. The Type of Ground Truth Used

The "ground truth" for the tests performed is based on:

Established Standards/Specifications: For parameters like cooling/warming rates, dimensional requirements, tensile strength, endotoxin levels, and sterility, the ground truth is defined by pre-determined numerical specifications or industry standards that the device must meet.
Biological Outcomes: For the Mouse Embryo Assay, the ground truth is the successful development of embryos to a certain stage (≥80% of 1-cell control embryos develop at 96 hours), which is a direct biological efficacy measure.

8. The Sample Size for the Training Set

This information is not applicable/not provided. This device is a physical medical device and does not involve machine learning or AI, thus there is no "training set."

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

This information is not applicable/not provided as there is no training set for this type of device.

Summary

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

March 14, 2016

KITAZATO BioPharma Co., Ltd. % Richard A. Vincins, CBA, CQA, RAC (US,EU) Vice President, Quality Assurance Emergo Global Consulting, LLC 816 Congress Avenue, Suite 1400 Austin, TX 78701

Re: K153027

Trade/Device Name: Cryotop® US Regulation Number: 21 CFR§ 884.6160 Regulation Name: Assisted Reproduction Labware Regulatory Class: II Product Code: MOK Dated: February 9, 2016 Received: February 12, 2016

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 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 - Richard A. Vincins, CBA, CQA, 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 contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

Herbert P. Lerner -S

for 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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Indications for Use

510(k) Number (if known) K153027

Device Name Cryotop®US

Indications for Use (Describe)

The Cryotop®US 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)

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510(k) Summary

Cryotop®US

K153027

1. Submission Sponsor

KITAZATO BioPharma Co., Ltd.

81 Nakajima, Fuji-city

Shizuoka 416-0907

JAPAN

Phone number: +(81) 545-66-2202

Contact: Futoshi Inoue

Title: President

2. Submission Correspondent

Emergo Global Consulting, LLC

816 Congress Avenue, Suite 1400

Austin, TX 78701

Office Phone: (512) 327 - 9997

Contact: Richard A. Vincins, Vice President, Quality Assurance/Regulatory Affairs

Email: project.management@emergogroup.com

3. Date Prepared

March 9, 2016

4. Device Identification

Trade/Proprietary Name:	Cryotop®US
Common/Usual Name:	Cryopreservation Storage Device
Classification Name:	Assisted Reproduction Labware
Regulation Number:	884.6160

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Product Code:

Device Class: Class II

Classification Panel: Obstetrics/Gynecology

MOK

5. Legally Marketed Predicate Device

K122982, CRYOLOCK™, BioTech Inc.

6. Device Description

7. Indication for Use Statement

The Cryotop®US 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. Substantial Equivalence Discussion

The following Table 1 compares the CryotopUS to the predicate device with respect to indications for use, principles of operation, technological characteristics, and performance testing. The comparison of the devices provides more detailed information regarding the basis for the determination of substantial equivalence.

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Manufacturer	Kitazato BioPharma Co.,Ltd.	BioTech Inc.	SignificantDifferences
Trade Name	Cryotop®US	CRYOLOCK™
510(k) Number	Not assigned	K122982
Product Code	MQK	MQK	Same
Regulation Number	884.6160	884.6160	Same
Regulation Name	Assisted ReproductionLabware	Assisted ReproductionLabware	Same
Indications for Use	The Cryotop®US is acryopreservation storagedevice that is intendedfor use in vitrificationprocedures to containand maintain human 4-8cell and blastocyst stageembryos	The CRYOLOCK™ is acryopreservation storagedevice that is intendedfor use in Vitrificationprocedures to containand maintain human 1-cell stage embryos	Similar; theindications for use areboth for thevitrification andstorage of humanembryos.
Mechanism of Action	Vitrification Method	Vitrification Method	Same
TechnologyOverview	The CryotopUS isdesigned to contain,freeze and maintainembryos. The deviceconsists of a two pieceassembly comprised ofthe main part containingthe fine tip film area andthe "straw." The handleshaft and straw aredesigned to be closedsystem. The straw isweighted to allow properalignment in the storagecontainer. TheCryotopUS device ispackaged in a singlebarrier sterilizationpouch.	The Cryolock is designedto contain, freeze andmaintain embryos. Thedevice is a square shapestick with four flatsurfaces. The device iscomposed of two pieceassembly with the mainpart for the embryoplacement and thehandle shaft and capdesigned to be a closedsystem. The CryoLockdevice is packaged in asingle barrier sterilizationpouch.	Same
Manufacturer	Kitazato BioPharma Co.,Ltd.	BioTech Inc.	SignificantDifferences
Trade Name	Cryotop®US	CRYOLOCK™
MaterialComposition	PET, ABS, Polypropylene	PET, Polypropylene	Similar; both devices are made of medical grade plastics that are commonly used.
Sterile	Radiation, SAL 10-6	Radiation, SAL 10-6	Same
Single-Use	Yes	Yes	Same
Shelf Life	3 years	3 years	Same
Cooling Rate	3,000°C/min	1,494°C/min	Different; though the cooling rate is different, non-clinical performance testing from both devices support intended use.
Rewarming Rate	44,000°C/min	21,000°C/min	Different; though the warming rate is different, non-clinical performance testing from both devices support intended use.
Contact withWarming Medium	The tip (film) and the shaft of CryotopUS are taken out from the straw. Directly immerse the tip (film) into thawing solution	The tip (film) and the shaft of Cryolock are taken out from the body. Directly immerse the tip (film) into thawing solution.	Same
Performance Testing	Passed	Passed	Same
Mouse EmbryoTesting	Passed	Passed	Same
Sterility ValidationTesting	Passed	Passed	Same

Table 1– Comparison of Characteristics

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The technological characteristics of the CryotopUS are comparable to the predicate device. The subject device does not raise any new issues of safety or effectiveness based on the similarities to the predicate device.

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9. Non-Clinical Performance Data

As part of demonstrating substantial equivalence to the predicate device, Kitazato BioPharma completed a number of non-clinical performance tests. The CryotopUS device meets all the requirements for overall design, sterilization, and performance testing results, confirming that the design output meets the design inputs and specifications for the device.

The CryotopUS device passed all the testing in accordance with internal requirements and applicable standards that is shown below to support substantial equivalence of the subject device:

. 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
. Durability Testing: No burst or liguid nitrogen inside the straw after 30 second immersion
. 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
. Shelf life testing
. Package integrity testing

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 CryotopUS device.

10. Conclusion

The results of the testing described above provide reasonable assurance that the CryotopUS is as safe and effective as the predicate device and supports a determination of substantial equivalence.

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.