(61 days)
Hyaluronidase Solution is intended for use in assisted reproductive technology procedures involving the manipulation of gametes or embryos. Specifically, Hyaluronidase Solution is intended for use in removing cumulus cells surrounding oocytes (denudation) in preparation for ICSI or other ART procedures.
Hyaluronidase Solution is a enzymatic solution containing 80 U/mL of bovine derived hyaluronidase in a HEPES buffered HTF Medium supplemented with 5.0 mg/mL (or 0.5%) therapeutic grade human serum albumin (HSA) and 10µg/mL gentamicin sulfate.
Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the Hyaluronidase Solution:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Support embryonic growth (absence of toxicity) | Assured by Mouse Embryo Assay (prior to release) |
| Removal of cumulus cells within 30-60 seconds (denudation) | Enzymatic digestion and removal occur within 30-60 seconds |
| No toxic components present | Assured by Mouse Embryo Assay (prior to release) |
| Suitability for intended use (denudation for ART procedures) | Validated by historical clinical use and performance testing |
| Meets criteria outlined in Notice of Final Rule, 63 FR 48428, Docket 97N-0335 | Conclusion states the device meets these criteria |
Note: The document does not explicitly list numerical acceptance criteria in a table format. The criteria are inferred from the "Performance Data" and "Conclusion" sections. For example, "support embryonic growth" is an implied criterion, and the "Mouse Embryo Assay" is the test mechanism.
2. Sample Size Used for the Test Set and Data Provenance
The document does not specify a distinct "test set" in the conventional sense (e.g., a specific number of oocytes or embryos used in a formal clinical trial for this submission).
- Sample Size: Not explicitly stated as a separate "test set" for the current submission. The "Mouse Embryo Assay" is mentioned, but its sample size for the purpose of this submission is not detailed. The "equivalent of Hyaluronidase Solution" has been used in "a variety of clinical settings for a number of years," implying historical clinical data but without specific sample sizes or structured test sets for this particular submission.
- Data Provenance: The document refers to the "equivalent of Hyaluronidase Solution" being used in "clinical settings," suggesting real-world use. This points towards retrospective observational data or historical experience. No specific country of origin is mentioned for this historical use, but the submitting company is US-based.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable for this submission. The "ground truth" for regulatory approval here is primarily based on pre-clinical lab assays (Mouse Embryo Assay) and historical clinical performance of similar products, rather than a human expert consensus on diagnostic results.
4. Adjudication Method for the Test Set
Not applicable. There's no human expert adjudication process described for the performance data presented.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. An MRMC comparative effectiveness study was not performed. This type of study is more common for diagnostic imaging AI devices where human reader performance is a key metric.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, in essence. The "Performance Data" section describes a standalone assay (Mouse Embryo Assay) that the product undergoes prior to release to market. This assay directly assesses the product's biological impact (support for embryonic growth, absence of toxicity) independent of human intervention in its evaluation for the purpose of this submission. The enzymatic action for denudation is also an inherent, standalone function of the solution.
7. The Type of Ground Truth Used
The ground truth used is a combination of:
- Biological Assay Results: Specifically, the Mouse Embryo Assay, which indicates the product's ability to support embryonic growth and its non-toxicity.
- Historical Clinical Use/Outcomes Data: The document states the "equivalent of Hyaluronidase Solution has been used in a variety of clinical settings for the same intended use for a number of years," implying that successful outcomes from these real-world uses serve as a form of ground truth for its efficacy and safety.
- Enzymatic Activity: The inherent function of the enzyme to digest cumulus cells is a direct measure of its intended effect.
8. The Sample Size for the Training Set
Not applicable. This device is a biological solution, not an AI/ML algorithm requiring a training set in the computational sense. The "training" here would be analogous to product development and formulation.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as it's not an AI/ML algorithm with a training set. The "ground truth" for the development and formulation of such biological media is established through biomedical research, standard laboratory protocols, and ensuring the final product meets functional and safety standards (e.g., appropriate enzyme concentration, sterility, pH, osmolality, and efficacy in cell removal and embryo viability). These are typically based on well-understood biological principles and established protocols in reproductive biology.
§ 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.