(196 days)
MediCult Vitrification Cooling is for vitrification of human, day 3 cleavage-stage embryos.
MediCult Vitrification Warming is for warming of vitrified human, day 3 cleavage-stage embryos.
The ORIGIO MediCult Vitrification Cooling (1228) and Warming (1229) media consist of two freezing and four warming media which are intended to be used sequentially. All the media are based on modified human tubal fluid (mHTF) buffered with HEPES supplemented with human serum albumin (12 mg/mL) and gentamicin sulphate (10 mg/L). MediCult Vitrification Cooling (1228) media contains the cryoprotectants ethylene glycol and 1,2propanediol. The concentration of the cryoprotectants increases in the two sequentially media, to increase the osmotic stress to withdraw water from the cell. The two sequential cooling media are; Vial 1: Equilibration Medium (1222) and Vial 2: Vitrification Medium (1223). The Equilibration Medium contains 7.5% (v/v) ethylene glycol and 7.5% (v/v) 1,2-propanediol. The Vitrification Medium contains 15% (v/v ) ethylene glycol and 15 % (v/v) 1,2-propanediol. The MediCult Vitrification Warming (1228) media contains sucrose in decreasing concentrations in four dilution steps. The four sequential warming media are: Vial I: Warming Medium (1224), Vial 2: Dilution Medium 1 (1225), Vial 3: Dilution Medium 2 (1226), and Vial 4: Washing Medium (1227). The four warming vials, Warming Medium, Dilution Medium 1, Dilution Medium 2, and Washing Medium contain 1M, 0.5M, 0.25M, and 0M sucrose, respectively. MediCult Vitrification Cooling (1228) and Warming (1229) are supplied in transparent polypropylene plastic vials with screw top closures in a volume of 1-2 ml. All the media are colorless, viscous solutions, sterile, and ready to use by professionals within assisted reproduction, All media are quality control tested before release for pH, sterility, mouse embryo assay, endotoxin. and osmolality.
The provided text describes the MediCult Vitrification Cooling and Warming media, which are intended for the vitrification and warming of human day 3 cleavage-stage embryos. The submission aims to demonstrate substantial equivalence to predicate devices (RapidVit™ Cleave and RapidWarm™ Cleave).
The document mentions "acceptance criteria" through comparison with existing devices and clinical outcomes but does not explicitly list specific acceptance criteria with defined thresholds. Instead, it argues for substantial equivalence based on similar intended use, technology, composition, and performance comparable to reported clinical outcomes.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document does not provide a formal table of explicit acceptance criteria with specific numerical thresholds. However, the implicit acceptance criteria are that the device should be "as safe and effective" as the predicate devices, and that clinical performance (delivery rates, miscarriage rates, pregnancy rates, implantation rates) should be within ranges considered acceptable or comparable to predicate devices and published literature.
| Implicit Acceptance Criterion | Reported Device Performance (MediCult Vitrification Cooling & Warming with 50 mg/mL HSA) | Comparison / Context |
|---|---|---|
| Delivery Rate per Started Thawing Cycle | 23.3% | Comparable to ASRM/SART (21%) and higher than ESHRE (12.0%) |
| Delivery Rate per Transfer Cycle | 23.7% | Comparable to ASRM/SART (23.5%) and higher than ESHRE (13.1%) |
| Miscarriage Rate | 6.3% | "In line with previous described miscarriage rates after vitrification" |
| Pregnancy Rate | 32% | Compared to 49.3% for predicate (Balaban et al., 2008) but "in line with pregnancy- and implantation rates reported in other published studies." |
| Implantation Rate | 15% | Compared to 29.7% for predicate (Balaban et al., 2008) but "in line with pregnancy- and implantation rates reported in other published studies." |
| Safety and Effectiveness (General) | Considered "as safe and effective as the predicate devices." | Based on similar intended use, technology, composition, quality control, and clinical data showing comparable outcomes to predicate and other published studies. |
| Bovine Embryo Performance (Blastocyst, Cleavage, Survival Rates) | "No significant differences" between new formulation (12 mg/mL HSA), older formulation (10 mg/mL Plasmanate), and 50 mg/mL HSA formulation. | Demonstrates consistency across formulations and predicate. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Human Clinical Study:
- Sample Size: Not explicitly stated as a number of cycles or embryos. The study reports percentages (23.3% per started thawing cycle, 23.7% per transfer cycles).
- Provenance: This was a retrospective clinical study. No country of origin is explicitly stated, but the contact person for the submission is in San Diego, CA (USA) and the submitting entity is in Denmark. The information suggests the data might be from a European context, particularly given the mention of previous commercial availability in Europe since 2006 for the former versions.
- Bovine Study:
- Sample Size: Not explicitly stated (number of bovine embryos used).
- Provenance: Preclinical bench testing. No country of origin stated.
3. 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)
This section is not applicable as the studies are clinical outcome studies for an in-vitro fertilization medium, not diagnostic studies requiring expert interpretation of images or other data for ground truth establishment. The "ground truth" here is the observed clinical outcomes (e.g., delivery rates, miscarriage rates, embryo development) which are objective physiological measures.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This is not applicable as there is no mention of an adjudication process. Clinical outcomes like delivery rates and miscarriage rates are typically objectively recorded rather than subject to expert adjudication in this context.
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
This is not applicable. This submission is for an Assisted Reproductive Technology (ART) media, not an AI-assisted diagnostic device that would involve human readers interpreting cases.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is not applicable. This is not an algorithm or AI device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- Clinical Study: Outcomes data was used. Specifically, clinical outputs such as delivery rates per started thawing cycle, delivery rates per transfer cycle, miscarriage rates, pregnancy rates, and implantation rates in human patients undergoing assisted reproduction.
- Preclinical (Bovine) Study: Embryo development outcomes were used, including blastocyst rates, cleavage rates, and survival rates. Morphology and development speed were also assessed.
8. The sample size for the training set
This is not applicable. There is no mention of a "training set" in the context of device development for this type of medical media. The clinical and preclinical studies described are for evaluation of the media, not for training a predictive model.
9. How the ground truth for the training set was established
This is not applicable as there is no training set.
§ 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.