(142 days)
This device is a vitrification storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell or blastocyst stage embryos.
Cryotec is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell or blastocyst stage embryos. It is designed to enable physicians and embryologists to preserve and to store vitrified embryos for assisted reproduction technology procedures. The Cryotec device is composed of a two piece assembly with a polyethylene terephthalate (PET) film sheet attached to a PET handle, and a weighted polyvinylchloride cap to cover the film sheet during handling and storage. During vitrification procedures, the film sheet is loaded with embryos, capped, and immersed in liquid nitrogen. The capped design creates a hermetic seal, resulting in a closed system keeping the film sheet and embryos isolated from liquid nitrogen. The cap is weighted to allow proper alignment in the storage container. The Cryotec device is provided sterile and is for single use only. The Cryotec device has been designed to maintain the integrity of the human embryos the freezing and thawing process.
The provided text describes the 510(k) premarket notification for the Cryotec device. This device is a cryopreservation storage device intended for use in vitrification procedures to contain and maintain human 4-8 cell or blastocyst stage embryos. The submission compares the Cryotec device to a legally marketed predicate device, the Kitazato CryotopUS (K153027), and presents non-clinical performance data to demonstrate substantial equivalence.
Here's a breakdown of the requested information based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
| Test | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Appearance | Particle free, no cracks | All devices are particle free with no cracks; met specifications |
| Durability | No breakage, no liquid nitrogen inside the cap | No breakage of the stick or cap, no liquid nitrogen inside the cap; met specifications |
| Tensile Strength | $\geq 5N$ | Tensile strength to withstand 5N; met specifications |
| Endotoxin | $< 0.5$ EU/device | Endotoxin values conform to the value < 0.5 EU/device; met specifications |
| Sterility | No growth | No microbial growth from sterility testing; met specifications |
| MEA (1-cell) | $\geq 80%$ blastocyst (1-cell) | $\geq 80%$ of 1-cell control embryos develop within 96 hours; met specifications |
| Cooling Rate | (Not explicitly stated for acceptance, but a specific rate was tested) | 1,500 °C/min.; met specifications |
| Warming Rate | (Not explicitly stated for acceptance, but a specific rate was tested) | 42,000 °C/min.; met specifications |
| Dimensional Testing | Passes outer diameter and length according to specifications | Passes outer diameter and length according to specifications |
| Shelf life testing | (No specific criteria mentioned, only that testing was performed) | Testing performed (results not detailed) |
| Package integrity testing | (No specific criteria mentioned, only that testing was performed) | Testing performed (results not detailed) |
2. Sample Size Used for the Test Set and Data Provenance
The document states, "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 Cryotec device."
- Sample Size for Test Set: Not explicitly stated as a fixed number. The tests are performed on "samples from routine manufactured lots," implying a continuous quality control process rather than a single fixed test set for premarket submission. No specific number of devices or embryos used for the performance testing or MEA is provided in this document.
- Data Provenance: The document does not specify the country of origin for the data or whether the studies were retrospective or prospective. Given that REPROLIFE Inc. is located in Japan and the correspondent is in the US, the testing could have occurred in either location or a third party.
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 primarily laboratory-based performance tests (e.g., physical characteristics, biological assays like MEA, sterility), which typically rely on standardized protocols and instrumental measurements rather than expert human interpretation for "ground truth" in the way a clinical image might. The Mouse Embryo Assay (MEA) results are stated as a percentage of blastocyst development, which is an objective biological outcome rather than an expert's subjective assessment.
4. Adjudication Method for the Test Set
This information is not applicable as the tests described are objective performance measurements (e.g., tensile strength, endotoxin levels, sterility, MEA blastocyst development rate) rather than subjective assessments requiring adjudication to establish ground truth.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not conducted or described. The submission focuses on non-clinical performance data to demonstrate substantial equivalence to a predicate device. The document does not mention any studies involving human readers or AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Not applicable. The Cryotec is a physical medical device (cryopreservation storage device), not an algorithm or AI system. Therefore, standalone algorithm performance is not relevant.
7. The Type of Ground Truth Used
The ground truth for the device's performance is established through objective laboratory measurements and biological assays, as opposed to expert consensus, pathology, or outcomes data from human patients. Examples include:
- Physical measurements (appearance, durability, tensile strength, dimensions).
- Chemical analysis (endotoxin levels).
- Microbiological testing (sterility).
- Biological assay (Mouse Embryo Assay, measuring blastocyst development).
8. The Sample Size for the Training Set
Not Applicable. The Cryotec is a physical medical device and does not involve an algorithm or AI that requires a "training set."
9. How the Ground Truth for the Training Set Was Established
Not Applicable. As mentioned above, there is no training set for this type of device.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 14, 2016
Reprolife Inc. % Diane Sudduth Sr. Consultant, RA/QA Emergo Group 816 Congress Avenue, Suite 1400 Austin, TX 78701
Re: K162051
Trade/Device Name: Cryotec Regulation Number: 21 CFR 884.6160 Regulation Name: Assisted Reproduction Labware Regulatory Class: Class II Product Code: MOK Dated: November 11, 2016 Received: November 14, 2016
Dear Diane Sudduth,
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. 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
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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,
Joyce M. Whang -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)
Device Name Cryotec
Indications for Use (Describe)
This device is a vitrification storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell or 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
for
CRYOTEC
K162051
1. Submission Sponsor
REPROLIFE Inc. 2-5-5-8F, Shinjuku Shinjuku-ku, Tokyo 160-0022 JAPAN Phone: +(81) 3-5925-8931 Contact: Koichi Takeda, Director, Global Certification Division
2. Submission Correspondent
Emergo Global Consulting, LLC 2500 Bee Cave Road Building 1, Suite 300 Austin, TX 78746 Office Phone: (512) 327 -9997 Contact: Diane Sudduth, Sr. Consultant RA/QA Email: project.management@emergogroup.com
3. Date Prepared
12/12/2016
4. Device Identification
| Trade/Proprietary Name: | Cryotec |
|---|---|
| Common/Usual Name: | Cryopreservation storage device |
| Classification Regulation: | 884.6160 |
| Classification Name: | Assisted Reproduction Labware |
| Product Code: | MQK (Labware, Assisted Reproduction) |
| Device Class: | Class II |
| Classification Panel: | Obstetrics and Gynecology |
5. Legally Marketed Predicate Device(s)
Kitazato, CryotopUS, K153027. The predicate device has not been subject to a design-related recall.
6. Device Description
Cryotec is a cryopreservation storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell or blastocyst stage embryos. It is designed to enable physicians and embryologists to preserve and to store vitrified embryos for assisted reproduction technology procedures.
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The Cryotec device is composed of a two piece assembly with a polyethylene terephthalate (PET) film sheet attached to a PET handle, and a weighted polyvinylchloride cap to cover the film sheet during handling and storage. During vitrification procedures, the film sheet is loaded with embryos, capped, and immersed in liquid nitrogen. The capped design creates a hermetic seal, resulting in a closed system keeping the film sheet and embryos isolated from liquid nitrogen. The cap is weighted to allow proper alignment in the storage container. The Cryotec device is provided sterile and is for single use only. The Cryotec device has been designed to maintain the integrity of the human embryos the freezing and thawing process.
The specifications for the Cryotec are as follows:
| Appearance: | Particle free, no cracks |
|---|---|
| Durability: | No breakage, no liquid nitrogen inside the cap |
| Tensile Strength: | $\geq 5N$ |
| Endotoxin: | $<$ 0.5 EU/device |
| Sterility: | No growth |
| MEA (1-cell): | $\geq$ 80% blastocyst |
7. Indication for Use Statement
This device is a vitrification storage device that is intended for use in vitrification procedures to contain and maintain human 4-8 cell or blastocyst stage embryos.
8. Substantial Equivalence Discussion
The following table compares the Cryotec to the predicate device (Cryotop®US) with respect to intended use, technological characteristics and principles of operation, providing more detailed information regarding the basis for the determination of substantial equivalence.
| Manufacturer | KITAZATO BioPharma Co., | REPROLIFE Inc. | |
|---|---|---|---|
| Trade Name | Cryotop®US | Cryotec | Comparison |
| 510(k) Number | K153027 | K162051 | - |
| Product Code | MQK | MQK | - |
| Regulation Number | 884.6160 | 884.6160 | - |
| Regulation Name | Assisted Reproduction | Assisted Reproduction Labware | - |
| Indications for Use: | The CryotopUS is acryopreservation storagedevice that is intended foruse in vitrificationprocedures to contain andmaintain human 4-8 celland blastocyst stageembryos. | This device is a vitrificationstorage device that isintended for use invitrification procedures tocontain and maintain human4-8 cell or blastocyst stageembryos. | Same |
Comparison of Characteristics
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| Overall Design | The device consists of a twopiece assembly comprised ofthe main part containing thefine tip film area and the"straw." The straw is designedto be sealed. The straw isweighted to allow properalignment in the storagecontainer. The CryotopUSdevice is packaged in a singlebarrier sterilization pouch. | The device is a square shapestick with four flat surfaces. Thedevice is composed of twopiece assembly with the film forembryo placement and handleshaft and weighted capdesigned to be a closed system.The Cryotec device is packagedin a single barrier sterilizationpouch. | Similar |
|---|---|---|---|
| MaterialComposition | PET, ABS, Polypropylene | PET | Different |
| Sealing Mechanism | The shaft handle contains ataper and stop. When insertedinto the straw, a hermeticallysealed closed system isformed. | The shaft is inserted into strawto form a hermetic seal creatinga closed system. | Same |
| Method of Action | Vitrification Method | Vitrification Method | Same |
| Sterilization method | Radiation, SAL 10-6 | Radiation, SAL 10-6 | Same |
| Cooling Rate | 3,000°C/min | 1500°C/min | Different |
| Rewarming Rate | 44,000°C/min | 42,000°C/min | Different |
| Rewarming method | The tip (film) and the shaft ofCryotopUS are taken out fromthe straw. Directly immersethe tip (film) into thawingsolution. | The tip (film) and theshaft ofCryotec are taken out from thecap. Directly immerse the tip(film) into thawing solution | Same |
| Shelf life | 3 years | 2 years | Different |
| Mouse Embryo | ≥80% blastocyst (1-cell) | ≥80% blastocyst (1-cell) | Same |
| Endotoxin | 0.5 EU/device | 0.5 EU/device | Same |
The subject and predicate device have the same intended use – vitrification and storage of 4-8 cell or blastocyst stage embryos.
The technological characteristics are different – the subject device has a different material composition, cooling rate, warming rate, and shelf life. However, different types of safety or effectiveness questions are not raised by these differences in technological characteristics. Nonclinical performance data has been provided to evaluate the effect of the different technological characteristics of the subject device.
9. Non-Clinical Performance Data
The Cryotec device conforms to product quality test specifications: appearance, dimension, durability, tensile strength, endotoxin and Mouse Embryo Assay. The Cryotec 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 1,500 °C/min.; met specifications ●
- Warming Rate Testing: Warming rate of 42,000 °C/min.; met specifications ●
- Visual Inspection: All devices are particle free with no cracks; met specifications ●
- Dimensional Testing: Passes outer diameter and length according to specifications
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- . Durability Testing: Following immersion into liquid nitrogen, no breakage of the stick or cap, no liquid nitrogen inside the cap; met specifications
- Mechanical Tensile Testing: Tensile strength to withstand 5N; met specifications
- Endotoxin Testing: Endotoxin values conform to the value < 0.5 EU/device; met specifications
- Sterility Testing: No microbial growth from sterility testing; met specifications
- . Mouse Embryo Assay: ≥80% of 1-cell control embryos develop within 96 hours; met specifications
- . 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 Cryotec device.
11. Statement of Substantial Equivalence
The results of the testing described above provide reasonable assurance that the Cryotec is as safe and effective as the predicate device and supports a determination of substantial equivalence.
§ 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.