(111 days)
The Eeva System is indicated to provide adjunctive information on events occurring during the first two days of development that may predict further development to the blastocyst stage on Day 5 of development. This adjunctive information aids in the selection of embryo(s) for transfer on Day 3 when, following morphological assessment on Day 3, there are multiple embryos deemed suitable for transfer or freezing. The device may also be used to collect additional time-lapse images until Day 5 of development for embryos not selected for transfer, to allow monitoring of continued embryo development.
The Eeva™ System is an Assisted Reproduction Embryo Image Assessment System (21 CFR 884.6195), installed in an IVF lab and used by embryologists and other IVF professionals. None of the System components have an individual, prior 510(k) clearance. Eeva System, Model EVS210 requires the use of the 12-microwell configuration of the Eeva™ Dish (K141663, also referred to as the "dish"), which is placed on the Eeva Scope (an assisted reproductive microscope). The Eeva Scopes are placed in commercially-available standard-sized incubators. The microscope employs high resolution time-lapse imaging to record an embryo's development during its first two days of incubation. Automated measurements of cell division timing parameters and the Eeva Test results are provided to the user after approximately 42 hours predicting the likelihood of whether an embryo will develop to the blastocyst stage. In Eeva System, Model EVS2210, image recording may continue through Day 5 of embryo development.
The Eeva™ System (EVS2210) provides adjunctive information on early embryo development (first two days) to predict progression to the blastocyst stage by Day 5. This information assists in selecting embryos for transfer on Day 3, especially when multiple suitable embryos are identified through morphological assessment.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly list acceptance criteria for specific performance metrics (like sensitivity, specificity, PPV, NPV) with predefined thresholds. However, it states that "simulated clinical testing (mechanical analysis) demonstrates that the Eeva System Model EVS2210 is informative, and the average specificity, sensitivity, positive predictive value, and negative predictive value performance are substantially equivalent in the adjunctive use of the subject and predicate devices." This implies that the performance of the Eeva System (EVS2210) closely matched that of its predicate device, Eeva System (EVS2000).
The "Algorithm Software Validation" and "Simulated Clinical Use" tests aimed to evaluate the ability of the Eeva System software to predict blastocyst formation and its clinical performance, including determination of sensitivity, specificity, positive predictive value, negative predictive value, and odds ratio.
Since the document asserts substantial equivalence, the implied acceptance criteria are that the EVS2210's performance metrics (sensitivity, specificity, PPV, NPV, odds ratio) should be comparable to or not worse than those of the predicate device (EVS2000).
| Metric | Acceptance Criteria (Implied, relative to predicate) | Reported Device Performance (Implied) |
|---|---|---|
| Blastocyst Prediction | "informative" and "substantially equivalent" to predicate device EVS2000 | Met, based on substantial equivalence claim |
| Sensitivity | "substantially equivalent" to predicate device EVS2000 | Met, based on substantial equivalence claim |
| Specificity | "substantially equivalent" to predicate device EVS2000 | Met, based on substantial equivalence claim |
| Positive Predictive Value | "substantially equivalent" to predicate device EVS2000 | Met, based on substantial equivalence claim |
| Negative Predictive Value | "substantially equivalent" to predicate device EVS2000 | Met, based on substantial equivalence claim |
| Odds Ratio | "substantially equivalent" to predicate device EVS2000 | Met, based on substantial equivalence claim |
2. Sample size used for the test set and the data provenance
The document mentions "Simulated Clinical Use" for evaluation but does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It refers to "clinical data submitted for the predicate device" as being "representative of expected safety and effectiveness of the Eeva System Model EVS2210," but this doesn't specify if new data was used for the EVS2210's simulated clinical use or if it entirely leveraged the predicate's data.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not specify the number or qualifications of experts used to establish the ground truth for the "Simulated Clinical Use" test set.
4. Adjudication method for the test set
The document does not describe any adjudication method used for the test set.
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
The document does not mention a multi-reader multi-case (MRMC) comparative effectiveness study, nor does it describe an effect size for human reader improvement with or without AI assistance. The device provides "adjunctive information" to aid embryologists, suggesting it's intended for human-in-the-loop use, but a formal MRMC study is not detailed.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
The "Simulated Clinical Use" is described as evaluating "clinical performance of the Eeva System software including determination of sensitivity, specificity, positive predictive value, negative predictive value, and odds ratio." This suggests a standalone evaluation of the algorithm's performance in predicting blastocyst formation. The device provides "adjunctive information," implying its output is then used by an embryologist. Therefore, a standalone evaluation of the software's predictive capability appears to have been performed.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth used for the "Algorithm Software Validation" and "Simulated Clinical Use" tests was the "blastocyst formation." This is an objective biological outcome (whether an embryo develops to the blastocyst stage by Day 5).
8. The sample size for the training set
The document does not provide information regarding the sample size for the training set used for the Eeva System's algorithm.
9. How the ground truth for the training set was established
The document does not provide information on how the ground truth for the training set was established. It only mentions that the device evaluates cell division timing parameters to predict blastocyst formation.
§ 884.6195 Assisted Reproduction Embryo Image Assessment System.
(a)
Identification. An Assisted Reproduction Embryo Image Assessment System is a prescription device that is designed to obtain and analyze light microscopy images of developing embryos. This device provides information to aid in the selection of embryo(s) for transfer when there are multiple embryos deemed suitable for transfer or freezing.(b)
Classification. Class II (special controls). The special control(s) for this device are:(1) Clinical performance testing must demonstrate a reasonable assurance of safety and effectiveness of the device to predict embryo development. Classification performance (sensitivity and specificity) and predictive accuracy (Positive Predictive Value and Negative Predictive Value) must be assessed at the subject and embryo levels.
(2) Software validation, verification, and hazard analysis must be provided.
(3) Non-clinical performance testing data must demonstrate the performance characteristics of the device. Testing must include the following:
(i) Total light exposure and output testing;
(ii) A safety analysis must be performed based on maximum (worst-case) light exposure to embryos, which also includes the safety of the light wavelength(s) emitted by the device;
(iii) Simulated-use testing;
(iv) Mouse Embryo Assay testing to assess whether device operation impacts growth and development of mouse embryos to the blastocyst stage;
(v) Cleaning and disinfection validation of reusable components;
(vi) Package integrity and transit testing;
(vii) Hardware fail-safe validation;
(viii) Electrical equipment safety and electromagnetic compatibility testing; and
(ix) Prediction algorithm reproducibility.
(4) Labeling must include the following:
(i) A detailed summary of clinical performance testing, including any adverse events;
(ii) Specific instructions, warnings, precautions, and training needed for safe use of the device
(iii) Appropriate electromagnetic compatibility information;
(iv) Validated methods and instructions for cleaning and disinfection of reusable components; and
(v) Information identifying compatible cultureware and explain how they are used with the device.