(86 days)
SAGE Vitrification Kit is intended for use in the vitrification of oocytes (MII), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.
SAGE Vitrification Warming Kit is intended for use in the thawing of virtified oocytes (MI), pronuclear (PN) zygotes through day 3 cleavage stage embryos and blastocyst stage embryos.
SAGE Vitrification Kit (ART-8025 and ART-8026): This kit includes two solutions (Equilibration Solution and Vitrification Solutions in the kit consist of a MOPS-buffered media containing non-essential and essential amino acids. gentamicin sulfate, and human serum albumin. These solutions also contain the cryoprotectants ethylene glycol, dimethyl sulfoxide (DMSO) and sucrose as described below:
Equilibration Solution (ES): 7.5% (v/v) each of DMSO and ethylene glycol. Vitrification Solution (VS): 15% (v/v) each of DMSO and ethylene glycol, and 0.6 M sucrose
SAGE Vitrification Warming Kit (ART-8030 and ART 8031): This kit includes three solutions (1.0M Sucrose Warming Solution [1.0 M WS], 0.5M Sucrose Warming Solution [0.5 M WS], and MOPS Solution [MS]). All solutions in the kit consist of a MOPS-buffered media containing non-essential and essential amino acids, gentamicin sulfate, and human serum albumin. These solutions contain the cryoprotectant sucrose at the level described in their names (i.e., 1.0M, 0.5M, or no sucrose).
Solutions in the SAGE Vitrification Kit and SAGE Vitrification Warming Kit are aseptically-filtered and are provided to users in either 5 ml Type 1 borosilicate glass vials with a rubber closure and an aluminum seal (ART-8025 and ART-8030) or 2 ml polypropylene vials with cap (ART-8026 and ART-8031). The solutions in ART-8025 and ART-8030 are single-use only devices, whereas solution in ART-8026 and ART-8031 are to be used within 7 days after opening.
The provided text is a 510(k) summary for the SAGE Vitrification Kit and SAGE Vitrification Warming Kit. It focuses on demonstrating substantial equivalence to a predicate device rather than presenting a study design with acceptance criteria for a new, AI/ML-driven medical device. Therefore, a direct response to your request, which implies an AI/ML device study, is not fully supported by the provided document.
However, I can extract the closest analogous information regarding "acceptance criteria" and "study that proves the device meets the acceptance criteria" from this document as understood within the context of reproductive media and supplements, not AI/ML devices.
Here's a breakdown based on the provided document, interpreting "acceptance criteria" as product specifications and "study" as performance testing and literature review to support substantial equivalence:
1. Table of Acceptance Criteria (Product Specifications) and Reported Device Performance
| Parameter | Acceptance Criteria (Subject Device Specification) | Reported Device Performance (Summary) |
|---|---|---|
| pH | 7.20-7.40 | Confirmed by testing (USP). |
| Osmolality (mOsm/kg) | ES: 2331-2849 | |
| VS: 5603-6849 | ||
| 1.0M WS: 1255-1535 | ||
| 0.5 M WS: 745-911 | ||
| MS: 257-273 | Confirmed by testing (USP). | |
| Endotoxin (EU/mL) | ). | |
| MEA 1-cell (% blastocysts at 96h) | ≥80% | Confirmed by Mouse Embryo Assay (MEA) 1-Cell. |
| Sterility | No microbial growth | Confirmed by sterility testing (USP) and Aseptic process validation testing (EN ISO 13408-1:2015 and EN ISO 13408-2:2011). |
| Shelf-life | 52 weeks (ART-8025/8030); 7 days after opening (ART-8026/8031) | ART-8025 and ART-8030 relied on testing from K073522. Real-time shelf-life testing was conducted on ART-8031 to ensure product specifications (Osmolality, Endotoxin, MEA, Sterility) were met at time zero and at 52 weeks (closed and open/simulated use vials). The success of this testing is implied by the conclusion of substantial equivalence. |
| Clinical Performance (Survival Rates) | Implicit acceptance of effective vitrification and warming for various stages | Oocytes: Literature 1: 94.1%; Literature 2: 75.0%; Literature 4: 92.1%; Literature 5: 90.5%. |
| Pronuclear (PN) Zygotes: Literature 6: 98.6%; Literature 7: 89.0%. | ||
| Cleavage-Stage Embryos: Literature 8: 97.1%. | ||
| Collapsed Blastocysts: Literature 9: 98.0%. | ||
| Clinical Performance (Fertilization Rates) | Implicit acceptance of effective vitrification and warming for various stages | Oocytes: Literature 1: 67.0%; Literature 2: 77.7%; Literature 5: 64.2%. |
| Clinical Performance (Pregnancy/Live Birth Rates) | Implicit acceptance of effective vitrification and warming for various stages | Oocytes: Literature 1: Clinical Pregnancy Rate 36.4%; Literature 2: Clinical Pregnancy Rate 33.3%; Literature 3: Pregnancy Rate 33.6%; Literature 4: Clinical Pregnancy Rate per embryo transfer 56.4%, Live Birth Rate per cycle 45.3%; Literature 5: Clinical Pregnancy Rate 40.9%. |
| Pronuclear (PN) Zygotes: Literature 6: Clinical Pregnancy Rate 21.6%; Literature 7: Clinical Pregnancy Rate 28.2%, 9 live birth events (18 infants). | ||
| Cleavage-Stage Embryos: Literature 8: Clinical Pregnancy Rate 41.6%. | ||
| Collapsed Blastocysts: Literature 9: Clinical Pregnancy Rate 35.3%. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not describe a traditional "test set" in the sense of a dedicated, pre-defined dataset for a single study, as would be done for an AI/ML device. Instead, it relies on a summary of non-clinical performance testing (in-house lab tests) and clinical performance data from published journal articles.
- Non-Clinical Test Samples: Not explicitly quantified in terms of sample size (e.g., number of batches, number of media samples tested for pH, osmolality, endotoxin). The Mouse Embryo Assay (MEA) states "1-cell MEA" but doesn't specify the number of mouse embryos or replicate tests.
- Clinical Performance Data: This is derived from 9 cited journal articles. The sample sizes vary per study and are reported within the summaries:
- Literature 1: 11 subjects, surplus MII oocytes (quantity not specified).
- Literature 2: 6 subjects, surplus MII oocytes (quantity not specified).
- Literature 3: General results/meta-analysis context, not a specific sample size.
- Literature 4: 2353 MII oocytes.
- Literature 5: 54 study subjects, 413 MII oocytes.
- Literature 6: 37 subjects, 74 embryos.
- Literature 7: 849 pronuclear-stage (PN) zygotes vitrified, 339 PN zygotes thawed over 103 cycles.
- Literature 8: 24 warming cycles (after OHSS risk).
- Literature 9: Control group of 102 warming cycles.
- Data Provenance: Not explicitly stated for all studies, but generally refers to clinical studies likely conducted in fertility clinics. The original journal articles (listed in Section XI) would contain this information. Given the context of the device and product development, it is likely these studies were retrospective or prospective clinical trials focusing on IVF outcomes. There is no mention of country of origin for the clinical data within this extract.
3. Number of Experts Used to Establish Ground Truth and Qualifications
This concept is not directly applicable to this type of device (reproductive media). The "ground truth" for non-clinical tests is established by laboratory measurements against predefined product specifications. For the clinical performance, the "ground truth" relates to actual biological outcomes (survival, fertilization, pregnancy, live birth), which are typically reported by clinicians and embryologists involved in the treatment, not "experts establishing ground truth for a test set" in the AI/ML sense. No specific number of experts or their qualifications for establishing ground truth are mentioned.
4. Adjudication Method for the Test Set
Not applicable. There is no "adjudication method" described as one would expect for an AI/ML device's test set. Clinical outcomes are reported as observed, not adjudicated by an independent panel.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
Not applicable. This device is a media kit, not an interpretation tool for image data. Therefore, no MRMC study was performed or described.
6. If a Standalone (Algorithm Only Without Human-in-the Loop Performance) was Done
Not applicable. This is not an AI/ML algorithm. The performance is of the media used by humans in a clinical setting.
7. The Type of Ground Truth Used
- Non-Clinical Performance:
- Physical/Chemical Properties: Measured values (pH, Osmolality, Endotoxin) compared to defined ranges.
- Biological Functionality: Mouse Embryo Assay (MEA) results (percentage blastocysts at 96h).
- Sterility: Absence of microbial growth.
- Clinical Performance:
- Clinical Outcomes Data: Survival rates, fertilization rates, clinical pregnancy rates, live birth rates following the use of the media in human oocyte/embryo vitrification and warming procedures. This is observational outcomes data from fertility treatments.
8. The Sample Size for the Training Set
Not applicable directly. This is not an AI/ML device that requires a "training set." The development of the media would involve research and formulation, but not in the sense of an AI model's training data.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for an AI/ML model for this device. The development of the media relies on cryobiology principles and empirical testing to achieve the desired cryoprotective properties and support oocyte/embryo viability.
§ 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.