(128 days)
HTF and Modified HTF are intended for use in assisted reproductive technology procedures that involve the manipulation of gametes or embryos. Specifically, HTF is intended for use as a culture medium for the embryo after fertilization, when used with an incubator, and as a medium to support in vitro fertilization. Modified HTF is intended for use as a sperm-processing medium in washing procedures, as an oocyte retrieval medium, for transport of the embryo, and as a support medium for implantation of the embryo. Both HTF and Modified HTF are intended to simulate the substances found in the human, female reproductive system.
HTF and Modified HTF (mHTF) are synthetic, defined media intended for use in assisted reproductive technology procedures. Both have been formulated to mimic the composition of the fluid found in human fallopian tubes. Modified HTF differs from HTF by the buffer system used. HTF uses a sodium bicarbonate buffering system, and is appropriate for those procedures requiring the use of a carbon dioxide atmosphere during incubation. Modified HTF utilizes a combined sodium bicarbonate/HEPES ([4-(2-hydroxyethyl)-1piperazineethanesulfonic acid]) buffer. This buffering system provides maintenance of physiological pH (7.2 to 7.4), and does not require the use of a carbon dioxide incubator.
Here's an analysis of the provided text regarding the acceptance criteria and study for Irvine Scientific's HTF and Modified HTF media:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Product is functional for intended use (support of embryonic growth) | Assured by Mouse Embryo Assay prior to release. |
| No toxic components present in the formulation | Assured by Mouse Embryo Assay prior to release. |
| Meets "criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335" | Verified through "performance testing, as well as a review of the historical information contained in professional literature." |
| Endotoxin levels within acceptable limits | Tested as a condition of release; results on lot-specific certificate. |
| Sterility | Tested as a condition of release; results on lot-specific certificate. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly define a "test set" in the context of a prospective clinical trial with a specified sample size. The evidence for performance relies on:
- Mouse Embryo Assay: This is a batch-release test, meaning it's performed for each lot of the product. The sample size for each assay is not specified.
- Historical Clinical Use: The document states, "HTF and modified HTF have been used in a variety of clinical settings, for their intended use, for a number of years. In that time, the products have become the standard media used for the retrieval, growth, storage and transport of human gametes and embryos." This indicates retrospective data (historical performance) primarily from clinical practice.
- Data Provenance: The general nature of "clinical settings" and "professional literature" suggests global or widespread use, but a specific country of origin for the historical data is not provided.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable in the conventional sense of establishing ground truth for a test set in a study. The product's performance is gauged against:
- The results of the mouse embryo assay (a biological test, not expert opinion).
- Its long-standing successful use in clinical practice, which implies implicit expert validation through widespread adoption and positive patient outcomes, but not through a formalized ground truth establishment process for a specific dataset.
4. Adjudication Method for the Test Set
Not applicable. There's no mention of a formal adjudication process involving multiple human reviewers for a specific "test set." The evaluation is based on the biological assay and historical clinical acceptance.
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
Not applicable. This submission is for a medical device (culture media), not an AI-powered diagnostic tool, and therefore, an MRMC study comparing human readers with and without AI assistance is not relevant.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This is not an algorithm or AI device. The mouse embryo assay, which acts as a standalone performance check for each lot, is a biological test, not an algorithm.
7. The Type of Ground Truth Used
- Biological Functionality (Mouse Embryo Assay): The "ground truth" for the lot release testing is the ability of the media to support mouse embryo growth and the absence of toxicity, as determined by a standardized biological assay. This is a form of outcome data (successful embryo development) in an animal model.
- Historical Clinical Outcomes/Expert Consensus (Implicit): For the broader acceptance criteria, the "ground truth" is based on the long-term, successful use of the products in human assisted reproductive technologies, which implicitly relies on the consensus of reproductive specialists regarding positive patient outcomes (pregnancies, births). There's no explicit "ground truth" dataset; it's established through years of clinical practice and acceptance.
8. The Sample Size for the Training Set
Not applicable. This is not an AI/machine learning device that requires a training set. The "training" for the product's development would have been empirical (trial and error during formulation) and based on scientific understanding, rather than statistical data training.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as no training set for an AI/ML algorithm is involved.
§ 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.