(187 days)
ISM1+: For culture of embryos. To be used in culture after fertilization in Universal IVF Medium (K 991279) up to Day3 to 6- to8-cell stage, followed by extended culture in ISM2+ or by transfer in UTM+.
ISM2+: For culture of embryos. To be used in culture from 6- to 8-cell stage on Day3 to blastocyst stage on day 5, followed by transfer in UTM+. ISM2+ shall be used after ISM1+.
UTM+: For transfer of embryos cultured in ISM1+ or ISM2+.
ISM1+, ISM2+, and UTM+ are sequential media for the culture and transfer of embryos. Their composition includes physiological salts, sodium bicarbonate, Penicillin/Streptomycin, HSA, Glucose and derived metabolites, Nucleosides, Non-essential amino acids, Essential amino acids, Phenol Red, and Vitamins. UTM+ also contains Hyaluronate.
Here's a breakdown of the acceptance criteria and the study information for the ISM1+, ISM2+, and UTM+ media, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Set by Sponsor) | Reported Device Performance (from studies) |
|---|---|
| Product Testing Controls (per batch): | |
| Sterility satisfactory | Certificate of Analysis available for each batch |
| pH within range | Certificate of Analysis available for each batch |
| Osmolality within range | Certificate of Analysis available for each batch |
| Endotoxin ≤ 0.1 EU/ml | Certificate of Analysis available for each batch |
| Mouse Embryo Assay: | |
| ISM1+ & ISM2+: Blastocyst rate > 70% (one-cell assay) | Certificate of Analysis available for each batch |
| UTM+: Blastocyst rate > 80% (two-cell assay) | Certificate of Analysis available for each batch |
| Clinical Equivalence: | |
| Equally effective to original ISM1/ISM2 media (modified versions of which ISM1+/ISM2+ are) | Clinical study concluded "two versions were equally effective." Also, "no registered complaints and no evidence that the product has been the cause of any serious adverse events." |
| Substantively equivalent to Vitrolife's G1.2-G2.2 sequential culture system | Two prospective studies showed equivalence to G1.2/G2.2 media systems. |
| Effective for development of embryos for Day 2-3 transfer or Day 5 blastocyst transfer | Demonstrated in original ISM media multicenter trial and supported by equivalence studies. |
2. Sample Sizes and Data Provenance
- Test Set (Clinical Data for Original ISM):
- Sample Size: 466 cycles.
- Data Provenance: France, prospective multicenter trial.
- Test Set (Clinical Data for ISM1+/ISM2+ vs. Original ISM):
- Sample Size: Not specified (referred to as "a clinical study").
- Data Provenance: Not specified (implied to be clinical, likely related to the sponsor's efforts).
- Test Set (Clinical Data for ISM+ series vs. G1.2/G2.2):
- Sample Size: Not specified (referred to as "two prospective studies").
- Data Provenance: Not specified (implied to be clinical).
- Batch Release Testing (Mouse Embryo Assay):
- Sample Size: Not specified per batch, but it's a routine quality control test.
- Data Provenance: Laboratory testing by the manufacturer.
3. Number of Experts and Qualifications for Ground Truth
This information is not provided in the document. The studies are clinical trials involving patients and their outcomes, which serve as the "ground truth" for effectiveness in supporting embryo development and transfer. The assessment of embryo viability and success is performed by clinicians (e.g., embryologists, IVF specialists), but their specific qualifications and number are not detailed.
4. Adjudication Method for the Test Set
This information is not provided. Clinical outcomes (pregnancies, embryo development) were likely assessed by the involved clinical centers and compiled. There's no mention of a specific adjudication panel or method beyond what's inherent in clinical practice.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done. The studies described are clinical trials comparing the culture media's efficacy in achieving desired embryo development and pregnancy outcomes, not studies involving human readers interpreting outputs or effects of an AI system.
6. Standalone (Algorithm Only) Performance
- No, a standalone performance study was not done. The device is a culture medium, not an algorithm or AI system. Its performance is directly observed through biological outcomes in embryos.
7. Type of Ground Truth Used
- Clinical Outcomes: For the clinical studies, the ground truth was based on:
- Embryo development (cleavage, blastocyst formation).
- Pregnancy rates.
- Singleton vs. twin pregnancies.
- Absence of serious adverse events.
- Biological/Laboratory Standards: For the product testing controls (sterility, pH, osmolality, endotoxin, Mouse Embryo Assay), the ground truth was established against predefined acceptable ranges and biological performance thresholds (e.g., blastocyst rate > 70%).
8. Sample Size for the Training Set
- Not Applicable. This is a medical device (culture medium), not a machine learning model. Therefore, there is no "training set" in the context of AI.
9. How the Ground Truth for the Training Set Was Established
- Not Applicable. As there is no AI training set, this question does not apply.
§ 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.