(135 days)
Vit Kit® - Freeze, Vitrification Freeze Kit for Embryos (PN through Blastocyst Stage) is intended for use in the vitrification of pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.
Vit Kit® - Thaw, Vitrification Thaw Kit for Embryos (PN through Blastocyst Stage) is intended for use in the thawing and recovery of vitrified pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.
The five (5) media that comprise the two (2) kits, Vit Kit® - Freeze, Vitrification Freeze Kit for Embryos (PN through Blastocyst Stage) and the Vit Kit® - Thaw, Vitrification Thaw Kit for Embryos (PN through Blastocyst Stage) are all based upon the modified formulation of Medium 199. The Medium 199 is HEPES buffered and contains 20% (v/v) DSS, 35ug/mL gentamicin and varying concentrations of DMSO, EG and sucrose. The two (2) freeze, ES and VS, media in the Vit Kit® - Freeze, Vitrification Freeze Kit for Embryos (PN through Blastocyst Stage) are intended to be used sequentially, for the preparation for, and cryopreservation of, PN, day 3 cleavage stage embryos and blastocyst stage embryos. ES is used in preparation for freezing and contains 7.5 % (v/v) DMSO and EG. VS is to be used during cryostorage and contains 15% (v/v) DMSO and EG and 0.5M sucrose.
The three (3) thaw, TS, DS and WS, media in the Vit Kit®- Thaw, Vitrification Thaw Kit for Embryos (PN through Blastocyst Stage) are also intended for sequential use in the thawing and recovery of cryopreserved human embryo. The first medium used in the thawing process, TS, contains 1.0M sucrose. The second medium, DS, contains 0.5M sucrose. The third medium, WS, contains no sucrose.
The provided document is a 510(k) summary for the Vit Kit® - Freeze and Vit Kit® - Thaw products, which are media used for the vitrification and thawing of human embryos. The document focuses on demonstrating substantial equivalence to predicate devices rather than directly providing acceptance criteria and a rigorous study proving the device meets those specific acceptance criteria in the manner of a clinical trial for a diagnostic device.
However, based on the information provided, we can infer the acceptance criteria and the study design used to support the substantial equivalence claim. The primary acceptance criteria appear to be the successful outcome of assisted reproductive procedures (ARP) after using the vitrification and thawing kits, specifically focusing on births and ongoing pregnancies.
Here's an analysis based on the available text:
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the clinical outcomes presented to demonstrate substantial equivalence to predicate devices. The study results focus on successful pregnancies and live births following the use of vitrified/thawed embryos.
| Acceptance Criteria (Implied) | Reported Device Performance (Aggregate from various studies/predicates) |
|---|---|
| Successful births from vitrified pronuclear stage zygotes | 10 healthy births (19 babies = 1 singleton and 9 deliveries = 18 babies) for the specific use of Irvine Scientific's Vit Kit® for pronuclear zygotes, as reported in studies by Kumasako, et. al. and Al-Hasani, et. al. |
| Aggregate: Total of thirty (30) births (10 singletons; 9 deliveries = 2 singletons, 7 twins, 2 triplets; 11 deliveries = number of children from the deliveries not known) for vitrified pronuclear stage zygotes and day 3 embryos. | |
| Ongoing pregnancies from vitrified pronuclear stage zygotes | 52 ongoing pregnancies (37 for Kumasako, et. al.; 15 for Al-Hasani, et. al.) from vitrified pronuclear stage zygotes and day 3 embryos. |
| Ongoing pregnancies from vitrified 2PN embryos (general) | 52 ongoing pregnancies (37 pregnancies for Kumasako, et. al.; 15 pregnancies for Al-Hasani, et. al) reported following use of 2PN embryos. |
| Ongoing pregnancies from vitrified blastocysts (general) | 137 ongoing pregnancies (136 pregnancies for Kuwayama, et. al. ; 1 pregnancy for Oakes, et. al. 11). |
| Births from predicate device (RapidVit™ Cleave and RapidWarm™) | 8 births (2 sets of twins and 6 singletons). This is presented to show that the proposed device, based on similar technology, is suitable for its intended use, implying comparable outcomes. |
Note: The document presents clinical data in an aggregate form, citing various publications. It asserts that the proposed device is "substantially equivalent" to predicate devices based on this summarized clinical data, rather than presenting a direct comparative study of the new device against a predefined set of acceptance criteria. The underlying assumption is that if the predicate devices demonstrate these outcomes, and the new device is functionally and compositionally similar, it will achieve similar outcomes.
Study Information
The document describes clinical data that was "presented in the Comparison to Predicate Device summary presented on page 68" (which is not included in the provided text). This indicates a review of existing literature and clinical outcomes associated with the predicate devices and potentially similar vitrification technologies. It is not a prospective clinical trial specifically designed to test the new device against stringent acceptance criteria.
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Sample size used for the test set and the data provenance:
- Test Set Sample Size: Not a single "test set" in the traditional sense. The data points mentioned are aggregated from various published clinical studies regarding vitrification techniques and predicate devices.
- "thirty (30) births" from vitrified pronuclear stage zygotes and day 3 embryos.
- "fifty-two (52) ongoing pregnancies" from 2PN embryos (37 from one study, 15 from another).
- "one hundred-thirty seven (137) ongoing pregnancies" from blastocysts (136 from one study, 1 from another).
- Specifically for the new device's intended use for pronuclear zygotes: "ten (10) healthy births (19 babies = 1 singleton and 9 deliveries = 18 babies)" and "fifty-two (52) ongoing pregnancies."
- For the predicate device (RapidVit™ Cleave and RapidWarm™ Cleave K080446): "resulted in the births of two (2) sets of twins and six (6) singletons, a total of eight (8) births."
- Data Provenance: Retrospective, as the data is summarized from existing published articles (e.g., Al-Hasani, Kumasako, Kuwayama, Oakes). The countries of origin are not specified for each study but are implied to be international given the nature of scientific publications in this field.
- Test Set Sample Size: Not a single "test set" in the traditional sense. The data points mentioned are aggregated from various published clinical studies regarding vitrification techniques and predicate devices.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify a number of experts or their qualifications for establishing ground truth for the summarized clinical data. The data is drawn from published scientific literature, where the ground truth (e.g., live birth, ongoing pregnancy) would have been established by the clinical teams conducting those studies (e.g., reproductive endocrinologists, embryologists).
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- No adjudication method is mentioned as this is a summary of existing clinical outcome data, not a prospective study where independent review of specific cases would be performed for the purpose of the 510(k). The "adjudication" would have occurred as part of the internal processes of the original studies cited.
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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:
- No, an MRMC study was not done. This device is a medical media kit for embryo vitrification, not an imaging diagnostic device assisted by AI.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Not applicable. This device is a chemical media kit, not an algorithm.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth used is primarily outcomes data, specifically clinical outcomes such as live births and ongoing pregnancies, which are definitive endpoints in fertility treatments.
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The sample size for the training set:
- Not applicable in the context of device approval for a chemical media kit. There isn't a "training set" for an algorithm. The development of the media formulation would have involved internal R&D experiments and optimization, but not in the sense of a machine learning "training set".
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How the ground truth for the training set was established:
- Not applicable, as there is no "training set" in the context of an algorithmic device. The formulation of the media would have been based on scientific principles, prior research, and experimental validation in vitro to optimize cryoprotective properties, which are then ultimately validated by clinical outcomes data as presented.
§ 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.