(267 days)
The Vitrification Solution Set is intended for use in the virification of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.
The Warming Solution Set is intended for use in the thawing of vitrified occytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.
The Vitrification Solution Set and Warming Solution Set are intended for freezing and thawing oocytes and embryos for use in assisted reproductive technology (ART) procedures.
The Vitrification Solution Set consists of two media components, the Equilibration Solution (ES) and the Vitrification Solution (VS). The Warming Solution Set consists of three media components, the Thawing / Warming Solution (TS), Diluent Solution (DS), and Washing Solution (WS). All media are provided in 1.8 ml polypropylene vials with a polyethylene cap. All media in both sets undergo aseptic filtration and are single-use only.
The provided text describes the 510(k) premarket notification for a medical device called "Vitrification Solution Set and Warming Solution Set." This document focuses on demonstrating that the new device is substantially equivalent to a legally marketed predicate device. The information details non-clinical performance testing conducted to support this claim, but it does not involve a study with human subjects, nor does it establish ground truth from human experts, or conduct MRMC studies relating to human reader performance with or without AI assistance.
Therefore, I cannot provide details on the specific aspects of acceptance criteria and study design that involve human readers, expert consensus for ground truth on human data, or MRMC studies, as the provided document pertains to in-vitro reproductive media testing rather than a diagnostic or therapeutic device requiring such evaluation for human use.
However, I can extract the acceptance criteria and performance data for the device itself based on the non-clinical testing:
Acceptance Criteria and Reported Device Performance
The acceptance criteria are established for the characteristics of the vitrification and warming solutions themselves rather than for a diagnostic output interpreted by humans. The performance demonstrated that these criteria were met.
| Acceptance Criteria Category | Specific Acceptance Criteria | Reported Device Performance (Met) |
|---|---|---|
| Sterility | No growth (per USP <71>) | Met (demonstrated no growth) |
| Endotoxins | $\leq$ 0.5 EU/mL (LAL) | Met (demonstrated $\leq$ 0.5 EU/mL) |
| pH (all solutions) | 7.2 - 7.6 (per USP <791>) | Met (demonstrated pH within range) |
| Osmolality | ES: 2348-2596 mOsm/kgVS: 2316-2559 mOsm/kg (after 1:1 dilution)TS: 1613-1782 mOsm/kgDS: 831-928 mOsm/kgWS: 261-289 mOsm/kg | Met (demonstrated osmolality within specified ranges for all solutions) |
| Mouse Embryo Assay (MEA) | $\geq$ 80% embryos developed to expanded blastocyst at 96 hours (one-cell system) | Met (demonstrated $\geq$ 80% development to expanded blastocyst) |
| Shelf-life | 1 year (product specifications met at time 0 and after accelerated aging) | Met (supported a one-year shelf-life) |
| Transportation Testing | Maintain integrity after transportation conditions | Met (demonstrated compliance with ASTM D4169-22 and cap/seal leak testing) |
Note: The studies described here are non-clinical performance tests for an in-vitro reproductive media, not clinical studies involving human patients or the evaluation of an AI algorithm's diagnostic performance. Therefore, many of the requested points are not applicable to the provided document.
Here's an explanation of the non-applicable points from your request:
2. Sample size used for the test set and the data provenance:
- The "test set" here refers to batches of the manufactured vitrification and warming solutions used for quality control and shelf-life testing. The document doesn't specify the exact number of batches or samples tested for each criterion, but it implies standard QC procedures.
- Data provenance: Not explicitly stated, but assumed to be from ECMPC, LLC's internal lab testing in the US, as they are the submitter. The studies are non-clinical (laboratory-based), not based on retrospective or prospective patient data.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not Applicable. Ground truth in this context is established by laboratory measurements (e.g., pH meters, osmometers, bacterial cultures, microscopic evaluation in MEA) and adherence to established standards (USP, ASTM, ISO). There are no human experts establishing "ground truth" in the way radiologists would for medical images.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not Applicable. Adjudication methods like 2+1 or 3+1 are used in medical imaging studies where there's human interpretation of data and potential disagreement. Here, the "truth" is determined by objective scientific measurements and established pass/fail criteria.
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:
- Not Applicable. This is not a study of human reader perception or AI assistance. It's a performance evaluation of a chemical solution via in-vitro assays.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not Applicable. There is no algorithm being tested in this submission. The device is a chemical solution.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" for this device's performance is based on pre-defined laboratory assay results and specifications as per recognized standards (e.g., USP monographs for sterility, endotoxins, pH, osmolality; FDA guidance for Mouse Embryo Assay; ASTM standards for transportation).
8. The sample size for the training set:
- Not Applicable. There is no "training set" as this is not an AI or machine learning model.
9. How the ground truth for the training set was established:
- Not Applicable. No training set exists.
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August 27, 2024
ECMPC, LLC % Sarah Fitzgerald Senior Consultant Emergo by UL 2500 Bee Cave Road Building 1. Suite 300 Austin, Texas 78746
Re: K233846
Trade/Device Name: Vitrification Solution Set and Warming Solution Set (Models 120, 210, 220) Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MOL Dated: July 31, 2024 Received: July 31, 2024
Dear Sarah Fitzgerald:
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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"
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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See
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the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Michael T. Bailey -S
For Monica D. Garcia, Ph.D. Assistant Director DHT3B: Division of Reproductive, Gynecology, and Urology Devices OHT3: Office of Gastrorenal, ObGyn, General Hospital, and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K233846
Device Name
Vitrification Solution Set and Warming Solution Set, Models: 120, 210, 220
Indications for Use (Describe)
The Vitrification Solution Set is intended for use in the virification of oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.
The Warming Solution Set is intended for use in the thawing of vitrified occytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos, 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 - K233846
Vitrification Solution Set and Warming Solution Set
1. Submitter
ECMPC, LLC 22751 Professional Drive, Suite 220 Kingwood, TX 77339
Contact: Dr. José Gaytán Melicoff Phone: 281-570-6111 Email: jgaytan@ecmpcservices.com
2. Correspondent
Emergo Global Consulting, LLC 2500 Bee Cave Road Building 1, Suite 300 Austin, TX 78746
Contact: Sarah Marie Fitzgerald Office Phone: (512) 327-9997 Email: LST.US.EmergoFDASubmissions@ul.com
3. Date Prepared
August 21, 2024
4. Device Identification
Trade Name: Vitrification Solution Set and Warming Solution Set (Models 120, 210, 220) Common Name: Vitrification Cryopreservation Media Regulatory Class: Class II Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive Media and Supplements Product Code: MQL
5. Predicate Device
Vitrification Kit and Thawing Kit (K171748) by Kitazato Corporation
The predicate device has not been subject to a design related recall.
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6. Device Description
The Vitrification Solution Set and Warming Solution Set are intended for freezing and thawing oocytes and embryos for use in assisted reproductive technology (ART) procedures.
The Vitrification Solution Set consists of two media components, the Equilibration Solution (ES) and the Vitrification Solution (VS). The Warming Solution Set consists of three media components, the Thawing / Warming Solution (TS), Diluent Solution (DS), and Washing Solution (WS). All media are provided in 1.8 ml polypropylene vials with a polyethylene cap. All media in both sets undergo aseptic filtration and are single-use only.
7. Indication for Use
The Vitrification Solution Set is intended for use in the vitrification of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.
The Warming Solution Set is intended for use in the thawing of vitrified oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos, and blastocyst stage embryos.
8. Substantial Equivalence Discussion
A comparison of the intended use and technological characteristics of the subject device and the predicate device is shown in the table below:
| Attribute | Subject:Vitrification Solution Set andWarming Solution Set(K233846) | Predicate:Vitrification Kit and ThawingKit (K171748) | Comparison |
|---|---|---|---|
| Indications forUse | The Vitrification Solution Set isintended for use in thevitrification of oocytes (MII),pronuclear (PN) zygotesthrough day 3 cleavage stageembryos, and blastocyst stageembryos.The Warming Solution Set isintended for use in thethawing of vitrified oocytes(MII), pronuclear (PN) zygotesthrough day 3 cleavage stageembryos, and blastocyst stageembryos. | The Vitrification Kit is indicatedfor use in the preparation,vitrification and storage ofoocytes (MII), pronuclear (PN)zygotes through day 3 cleavagestage embryos, and blastocyststage embryos.The Thawing Kit is indicated foruse in the preparation andthawing of vitrified oocytes(MII), pronuclear (PN) zygotesthrough day 3 cleavage stageembryos, and blastocyst stageembryos. | There are differences inthe wording of theindications for usestatements for thesubject and predicatedevice; however, theintended uses of thesubject and predicatedevices are the same. |
| Sets /Components | Vitrification MediaWarming Media | Vitrification MediaThawing MediaCryotopRepro Plate 35 mm dish | Different: Thecomponents of thesubject and predicatedevices are not the same. |
| Attribute | Subject:Vitrification Solution Set andWarming Solution Set(K233846) | Predicate:Vitrification Kit and ThawingKit (K171748) | Comparison |
| Embryo Stage | Oocyte, PN through Blastocyst | Oocyte, PN through Blastocyst | Same |
| VitrificationMediaComponents | 2 – equilibration solution,vitrification solution | 3 – basic solution, equilibrationsolution, vitrification solution | Different: The number ofvitrification media of thesubject and predicatedevices are not the same.Differences invitrification solutions donot raise differentquestions of S&E. |
| WarmingMediaComponents | 3 – thawing solution, diluentsolution, washing solution | 3 –thawing solution, diluentsolution, washing solution | Same |
| VitrificationFormulation | HEPESHEPES sodium saltEthylene glycolDimethyl sulfoxideTrehaloseHydroxypropyl celluloseGentamicinMinimum Essential MediumPolyvinylpyrrolidoneSodium bicarbonate | Medium 199 HEPESEthylene glycolDimethyl sulfoxideTrehaloseHydroxypropyl celluloseGentamicin | Different: Theformulations of thesubject and predicatedevices are not the same.Differences in deviceformulations do not raisedifferent questions ofS&E. |
| Warming /ThawingFormulation | HEPESHEPES sodium saltHydroxypropyl celluloseTrehaloseMinimum Essential MediumPolyvinylpyrrolidoneSodium bicarbonateGentamicin | Medium 199 HEPESHydroxypropyl celluloseTrehaloseGentamicin | |
| Sterilization | Aseptic filtration | Aseptic filtration | Same |
| Sterility | No growth | Passes USP <71> | Same |
| Endotoxins | $≤$ 0.5 EU/ml (LAL) | $<$ 0.25 EU/ml (LAL) | Different: The endotoxinspecification of thesubject and predicatedevices are not the same.Differences in the stated |
| Attribute | Subject:Vitrification Solution Set andWarming Solution Set(K233846) | Predicate:Vitrification Kit and ThawingKit (K171748) | Comparison |
| endotoxin specificationsdo not raise differentquestions of S&E. | |||
| Mouse EmbryoAssay (MEA) | ≥ 80% embryos developed toexpanded blastocyst at 96hours | ≥ 80% development toblastocyst at 96 hours | Similar |
| pH | 7.20 - 7.60 | 7.20 - 7.60 | Same |
| Osmolality(mOsm/kg) | ES: 2348-2596VS: 2316-2559 after 1:1dilutionTS: 1613-1782DS: 831-928WS: 261-289 | Not available | Different: The osmolalityspecification of thesubject and predicatedevices are not the same.Differences in osmolalitydo not raise differentquestions of S&E. |
| Storage | 2-8°C | 2-8°C | Same |
| Packaging | Each solution is contained in1.8 mL polypropylene (PP)container and polyethylene(PE) screw caps molded with athermoplastic elastomer (TPE)layer. | Each solution is contained in1.5 mL or 4 mL plastic vials. | Different: The packagingof the subject andpredicate devices are notthe same. Differences inpackaging do not raisedifferent questions ofS&E. |
| Shelf-Life | 1 year | 1 year | Same |
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As shown in the table above, there are differences in the indications for use statements and technological characteristics of the subject and predicate devices. However, as stated in the table, the differences in indications for use do not represent a new intended use and the differences in technological characteristics do not raise different questions of safety and effectiveness.
9. Summary of Non-Clinical Performance Testing
To demonstrate safety and effectiveness of the Vitrification Solution Set and Warming Solution Set and to show substantial equivalence to the predicate device, the following non-clinical tests have been performed.
- . Aseptic processing and validation testing that met the requirements of ISO 13408-1:2008/Amd1:2013 and ISO 13408-2:2018. Testing was conducted on the subject device containing no antimicrobials.
- Shelf-life testing was conducted to support a one-year shelf-life for the subject devices through demonstration that the product specifications (shown below) were met at time 0 and after accelerated aging per ASTM F1980:21:
- Sterility per USP <71>: No growth -
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- -Endotoxin per USP <85>: ≤ 0.5 EU/mL
- pH per USP <791>: 7.2-7.6 for all solutions
- -Osmolality per USP <785>: see the table above for acceptance specifications
- -Mouse embryo assay per FDA guidance "Mouse Embryo Assay for Assisted Reproduction Technology Devices" (2021): One-cell system: ≥80% embryos developed to expanded blastocyst at 96 hours
- . Transportation testing per ASTM D4169-22 and cap/seal leak testing using a method equivalent to USP <1207.2> on transportation-conditioned devices.
10. Conclusion
The results of the performance testing described above demonstrate that the subject device is as safe and effective as the predicate device and supports a determination of substantial equivalence.
§ 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.