(184 days)
The Vitrification Kit is indicated for use in the preparation, vitrification and storage of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.
The Thawing Kit is indicated for use in the preparation and thawing of vitrified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.
The Vitrification and Thawing Kits are composed of a set of six media to vitrify and warm MII oocytes, and pronuclear (PN) zygotes through blastocyst stage embryos for Assisted Reproductive Technology (ART) procedures.
The Vitrification Kit includes three media components, Basic Solution (BS), Equilibration Solution (ES) and Vitrification Solution (VS), containing the cryoprotectants ethylene glycol, trehalose, and dimethyl sulfoxide. During the vitrification process, embryos are first exposed to ES and then to VS. In the case of the oocytes, use BS and ES. Using this methodology, the permeating cryoprotectants can replace water in the occyte, PN through blastocyst stage embryos prior to vitrification and storage in liquid nitrogen. The Vitrification Kit comes prepackaged with one 1.5 ml vial of BS and ES, two 1.5 ml vials of VS, 4 Cryotop devices (Cryotop CL, Cryotop SC, or Cryotop US), and 2 Repro Plates.
The Thawing Kit is composed of three media used stepwise for thawing cryoprotectants from vitrified oocytes, and PN through blastocyst stage embryos. The Thawing Kit is composed of TS (Thawing Solution), DS (Dilution Solution) and WS (Wash Solution). The Thawing Kit comes pre-packaged with two 4.0 ml vials of thawing solution, one 4.0 ml vial of dilution solution, one 4.0 ml vial of washing solution, one Repro Plate, and two 35 mm dishes.
All the media in the Vitrification Kit contain Gentamicin. The media in these kits undergo aseptic filtration, while storage devices and plates are sterilized by radiation.
The provided document describes the Vitrification Kit and Thawing Kit (K171748) and its substantial equivalence to a predicate device. Below is an attempt to extract the requested information, though it's important to note that this document is a 510(k) Summary, which focuses on demonstrating substantial equivalence rather than a full study report with detailed acceptance criteria and performance data in the format often associated with AI/software performance studies. The device is a "Reproductive Media and Supplements," which are chemical reagents, not an AI/software device, so many of the requested fields (like AI-specific performance metrics, reader studies, etc.) are not directly applicable.
Here's the information based on the provided text:
Acceptance Criteria and Device Performance
Since this is a submission for a "Reproductive Media and Supplements" kit, the acceptance criteria are related to the biological outcome (survival, development, etc.) of oocytes and embryos rather than typical device performance metrics like accuracy, sensitivity, or specificity of an AI algorithm. The performance is compared to similar existing products (predicate device or other vitrification media).
| Acceptance Criteria (Bench/Literature Study) | Reported Device Performance (as demonstrated by literature or similar device) |
|---|---|
| Oocyte Survival Rate (compared to surrogate device/vitrification media with serum substitute) | Comparable oocyte survival rate between a surrogate device (with similar formulation and cryoprotectants to the subject device) and vitrification media containing serum substitute supplement. Also, comparable oocyte survival rate to other methods of vitrification. |
| Implantation Rate (following vitrification using a surrogate device) | Comparable implantation rate between a surrogate device (with similar formulation and cryoprotectants to the subject device) and vitrification media containing serum substitute supplement. |
| Clinical Pregnancy Rate (following vitrification using a surrogate device) | Comparable clinical pregnancy rate between a surrogate device (with similar formulation and cryoprotectants to the subject device) and vitrification media containing serum substitute supplement. |
| Live Birth Rate (following vitrification using a surrogate device) | Comparable live birth rate between a surrogate device (with similar formulation and cryoprotectants to the subject device) and vitrification media containing serum substitute supplement. Birth rates following use of vitrified oocytes were shown to be comparable to the methods used in the predicate device. |
| Human Blastocyst Survival Rate (compared to surrogate device/vitrification media with serum substitute) | Comparable human blastocyst survival rate following vitrification between a surrogate device (with similar formulation to the predicate device) and vitrification media containing serum substitute supplement. |
| Fertilization Rate of Oocytes (following vitrification using methods similar to the subject device) | Fertilization rate comparable to fresh oocytes. |
| Quality Blastocyst Rate (following vitrification using methods similar to the subject device) | Quality blastocyst rate comparable to fresh oocytes. |
| Survival rates of oocytes and embryos (general consistency with normal ART procedures) | Consistent with normal ART procedures using similar IVF treatments and cryopreservation techniques. |
| Endotoxin (LAL methodology for Media) | < 0.25 EU/mL |
| Mouse Embryo Assay (development to blastocyst at 96 hours) | > 80% development to blastocyst at 96 hours |
| Sterility Testing | Passes |
| pH Test | 7.20 - 7.60 |
| Biocompatibility | Passes |
| Sterilization Validation, Packaging Validation, Performance (bench) testing (for identical device cleared under K160864, leveraged in this submission) | Passed all testing. |
Study Details
-
Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size: Not explicitly stated as a single "test set" number. The evidence comes from three published scientific papers.
- Literature 1 (Coello et al, 2016): Retrospective cohort study.
- Literature 2 (Mori et al, 2015): Not specified in the summary, but likely a study comparing different methods.
- Literature 3 (Inoue et al, 2014): Not specified.
- Data Provenance: Not explicitly stated for all, but Coello et al. is published in Journal of Assisted Reproduction Genetics, typically international. Mori et al. published in Reproductive BioMedicine Online. Inoue et al. in Low Temp Med. Specific countries of origin for the patient data are not detailed in this summary. The studies appear to be retrospective and prospective clinical/bench studies, but specific details for each are not fully provided in this summary.
- Sample Size: Not explicitly stated as a single "test set" number. The evidence comes from three published scientific papers.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
- Not applicable in the context of this device (Reproductive Media Kit). The "ground truth" for the performance claims would be the observed biological outcomes (survival, fertilization, development to blastocyst, pregnancy, live birth rates) reported in the referenced scientific literature, likely assessed by trained embryologists and clinicians.
-
Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Not applicable. This is not an AI/image analysis device requiring expert adjudication of outputs.
-
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
- Not applicable. This is not an AI device. The comparison is between different media formulations and vitrification methods.
-
If a standalone (i.e. algorithm only without human-in-the loop performance) was done
- Not applicable. This is not an AI/algorithm device.
-
The type of ground truth used (expert concensus, pathology, outcomes data, etc)
- The "ground truth" here is outcomes data and biological observations from clinical and laboratory studies reported in published literature, such as oocyte/embryo survival rates, fertilization rates, blastocyst development, implantation rates, clinical pregnancy rates, and live birth rates.
-
The sample size for the training set
- Not applicable. This is a medical device (chemical media), not an algorithm or AI model that requires a training set.
-
How the ground truth for the training set was established
- Not applicable. (See #7).
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December 14, 2017
Kitazato Corporation % Diane Sudduth Senior Consultant, RA Emergo Global Consulting, LLC 2500 Bee Cave Road, Building 1, Suite 300 Austin, TX 78746
Re: K171748
Trade/Device Name: Vitrification Kit and Thawing Kit Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MOL, MOK Dated: November 9, 2017 Received: November 13, 2017
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.
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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); 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.
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.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
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) K171748
Device Name Vitrification Kit and Thawing Kit
Indications for Use (Describe)
The Vitrification Kit is indicated for use in the preparation, vitrification and storage of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.
The Thawing Kit is indicated for use in the preparation and thawing of vitrified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
Vitrification Kit and Thawing Kit
K171748
1. Submission Sponsor
Kitazato Corporation
81 Nakajima, Fuji-city
Shizuoka 416-0907
JAPAN
Phone number: +(81) 546-66-2202
Contact: Futoshi INOUE
Title: President
2. Submission Correspondent
Emergo Global Consulting, LLC
2500 Bee Cave Road, Building 1, Suite 300
Austin, TX 78746
Office Phone: (561) 305-5075
Contact: Diane Sudduth, Senior Consultant, RA
Email: project.management@emergogroup.com
3. Date Prepared
14 December 2017
4. Device Identification
| Trade/Proprietary Name: | Vitrification Kit and Thawing Kit |
|---|---|
| Common/Usual Name: | Vitrification Cryopreservation Media |
| Classification Name: | Reproductive Media and Supplements |
| Classification Number: | 884.6180 |
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| Product Code: | MQL - Media, Reproductive |
|---|---|
| MQK – Labware, Assisted Reproduction | |
| Device Class: | Class II |
| Classification Panel: | Obstetrics/Gynecology |
5. Legally Marketed Predicate Devices
K160006, Vit Kit® - Vitrification Freeze Kit/ Vitrification Thaw Kit, Irvine Scientific Sales Co., Inc.
The predicate device has not been subject to a design-related recall.
Device Description 6.
The Vitrification and Thawing Kits are composed of a set of six media to vitrify and warm MII oocytes, and pronuclear (PN) zygotes through blastocyst stage embryos for Assisted Reproductive Technology (ART) procedures.
The Vitrification Kit includes three media components, Basic Solution (BS), Equilibration Solution (ES) and Vitrification Solution (VS), containing the cryoprotectants ethylene glycol, trehalose, and dimethyl sulfoxide. During the vitrification process, embryos are first exposed to ES and then to VS. In the case of the oocytes, use BS and ES. Using this methodology, the permeating cryoprotectants can replace water in the occyte, PN through blastocyst stage embryos prior to vitrification and storage in liquid nitrogen. The Vitrification Kit comes prepackaged with one 1.5 ml vial of BS and ES, two 1.5 ml vials of VS, 4 Cryotop devices (Cryotop CL, Cryotop SC, or Cryotop US), and 2 Repro Plates.
The Thawing Kit is composed of three media used stepwise for thawing cryoprotectants from vitrified oocytes, and PN through blastocyst stage embryos. The Thawing Kit is composed of TS (Thawing Solution), DS (Dilution Solution) and WS (Wash Solution). The Thawing Kit comes pre-packaged with two 4.0 ml vials of thawing solution, one 4.0 ml vial of dilution solution, one 4.0 ml vial of washing solution, one Repro Plate, and two 35 mm dishes.
All the media in the Vitrification Kit contain Gentamicin. The media in these kits undergo aseptic filtration, while storage devices and plates are sterilized by radiation. The specifications for the Vitrification Kit and Thawing Kit are listed in Table 1 below.
7. Indication for Use Statement
The Vitrification Kit is indicated for use in the preparation, vitrification and storage of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.
The Thawing Kit is indicated for use in the preparation and thawing of vitrified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.
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8. Substantial Equivalence Discussion
The following table compares the Vitrification Kit to the predicate devices with respect to indications for use, principles of operation, technological characteristics, materials, and performance testing. The comparison of the devices provides more detailed information regarding the basis for the determination of substantial equivalence. As noted in the table, there are differences in indications for use and technological characteristics between the subject and predicate devices; however, the differences indications for use do not represent a new intended use, and differences in the technological characteristics do not raise any different questions of safety or effectiveness as compared to the predicate device.
| Manufacturer | Kitazato Corporation | Irvine Scientific Sales Co., Inc. |
|---|---|---|
| Trade Name | Vitrification Kit and Thawing Kit | Vitrification Freeze Kit andVitrification Thaw Kit (Vit-Kit®-Thaw) |
| 510(k) Number | Not assigned | K160006 |
| Product Code | MQL, MQK | MQL |
| RegulationNumber | 884.6180 | 884.6180 |
| Regulation Name | Reproductive Media and Supplements | Reproductive Media and Supplements |
| Indications for Use | The Vitrification Kit is indicated for usein the preparation, vitrification andstorage of oocytes (MII),pronuclear(PN) zygotes through day 3cleavage stage embryos and blastocyststage embryos.The Thawing Kit is indicated for use inthe preparation and thawing ofvitrified oocytes (MII), pronuclear (PN)zygotes through day 3 cleavage stageembryos and blastocyst stageembryos. | Vit Kit® - Freeze (Vitrification FreezeKit) is intended for use in thevitrification of oocytes (MII),pronuclear (PN) zygotes through day 3cleavage stage embryos and blastocyststage embryos.Vit Kit® - Thaw (Vitrification Thaw Kit)is intended for use in the thawing ofoocytes (MII), pronuclear (PN) zygotesthrough day 3 cleavage stage embryosand blastocyst stage embryos. |
| Components of Kit | Vitrification MediaThawing Media | Vitrification Freeze KitVitrification Thaw Kit |
| Embryo Stage | Oocyte, PN through Blastocyst | Oocyte, PN through Blastocyst |
| Manufacturer | Kitazato Corporation | Irvine Scientific Sales Co., Inc. |
| Trade Name | Vitrification Kit and Thawing Kit | Vitrification Freeze Kit andVitrification Thaw Kit (Vit-Kit®-Thaw) |
| Principal ofOperation | Provides users with the ability tocryopreserve supernumerary oocytesor embryos created during the in vitrofertilization procedure and then to re-warm them for use at a future point intime | Provides users with the ability tocryopreserve supernumerary oocytesor embryos created during the in vitrofertilization procedure and then to re-warm them for use at a future point intime |
| VitrificationFormulation | In a Medium 199 HEPES bufferedMedium | In a Medium 199 HEPES bufferedMedium |
| Ethylene glycol | Ethylene glycol | |
| DMSO | DMSO | |
| Trehalose | Sucrose | |
| Hydroxypropyl Cellulose (HPC) | Dextran Serum Supplement (DSS) | |
| Gentamicin | Gentamicin | |
| Vitrification Steps | 2 Step | 2 Step |
| ThawingFormulation | In a Medium 199 HEPES bufferedMedium | In a Medium 199 HEPES bufferedMedium |
| Hydroxypropyl Cellulose (HPC) (v/v) | Dextran Serum Supplement (DSS) (v/v) | |
| Gentamicin | Gentamicin | |
| Trehalose | Sucrose | |
| Thawing Steps | 3 Step | 3 Step |
| Carton Packaging | Each solution is contained in plasticvials. Vials are packed in a card boardouter box with partition. | Each solution is contained in plasticvials. Vials are packed in a card boardouter box with partition. |
| CryopreservationStorage DeviceUsed With | Kitazato CorporationCryotop®CL-K112695Cryotop®SC - K140072Cryotop®US-K153027 | Irvine ScientificHSV Straw - K092398CryoTip - K041562 |
| Sterile | Solutions sterilized using asepticprocessing techniques throughfiltrationVial containers are sterilized viaradiation | Solutions sterilized using asepticprocessing techniques throughfiltrationVial containers are sterilized viaradiation |
| Manufacturer | Kitazato Corporation | Irvine Scientific Sales Co., Inc. |
| Trade Name | Vitrification Kit and Thawing Kit | Vitrification Freeze Kit andVitrification Thaw Kit (Vit-Kit®-Thaw) |
| Endotoxin | Endotoxin by LAL methodology <0.25EU/mL(LAL) for Media | Endotoxin by LAL methodology<0.25EU/mL) |
| Mouse EmbryoAssay | >80% development to blastocyst at 96hours | >80% one-cell 96 hours |
| Sterility Testing | Passes | Passes |
| pH Test | 7.20 - 7.60 | Not available |
| Biocompatibility | Passes | Passes |
| Storage | 2 – 8°C | 2 – 8°C |
| Shelf Life | 1 year | 1 year |
Table 5A - Comparison of Characteristics
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9. Non-Clinical Performance Data
The subject device is identical to the Kitazato Cryotop Vitrification and Thawing Kit cleared under K160864. Design verification tests were performed on the identical device cleared under K160864. Testing included sterilization validation, packaging validation, and performance (bench) testing. The device passed all the testing. Therefore, the information provided in K160864 was leveraged in this submission to support substantial equivalence of the Vitrification Kit and Thawing Kit.
10. Clinical Performance Data
The clinical information presented provides published papers that specifically identify vitrification/thawing media with HPC that are similar to or identical to the predicate device and the use of the Cryotop as the vitrification method for the cryopreservation of oocytes and blastocyst from human and mouse. A summary of the results are shown below:
- Literature 1: results of the study show comparable oocyte survival rate, implantation rate, clinical pregnancy rate, and live birth rate between a surrogate device (with similar formulation and cryoprotectants to the subject device) and vitrification media containing serum substitute supplement1
1 A combination of hydroxypropyl cellulose as supplementation for vitrification of human oocytes: a retrospective cohort study (Coello et al, Journal of Assisted Reproduction Genetics, 2016 March; 33(3): 413-421)
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- Literature 2: results of the study show that human blastocyst survival rate following vitrification was comparable between a surrogate device (with similar formulation to the predicate device) and vitrification media containing serum substitute supplement²
- . Literature 3: results of the study show comparable oocyte survival rate to other methods of vitrification and a fertilization rate and quality blastocyst rate as comparable to fresh oocytes. 3
Birth rates following use of vitrified oocytes as compared to the vitrification methods used in the predicate device were shown to be comparable. Each of the studies reported survival rates of oocytes and embryos that are consistent with normal ART procedures using similar IVF treatments and cryopreservation techniques.
11. Statement of Substantial Equivalence
The results of the performance testing described above demonstrate that the Vitrification Kit and Thawing Kit are as safe and effective as the predicate device and supports a determination of substantial equivalence.
? Hydroxypropyl cellulose as an option for sypprotectant solutions for embryo vitrification in human assisted reproductive technologies (Mori et al, Reproductive BioMedicine Online, 2015 June;30(6):613-21)
3 Efficiency of a Closed Vitrification System with Oocytes and Blastocysts (Inoue et al, Low Temp Med, 2014; 40(3): 53-59)
§ 884.6180 Reproductive media and supplements.
(a)
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.).(b)
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.