(128 days)
P-1® medium is intended for use in assisted reproductive technology procedures that involve the manipulation of gametes or embryos. Specifically, P-1® is intended for use as a culture medium through day three of embryo development.
P-1 medium is a synthetic, defined medium composed of a balanced mixture of salts and other nutrient substances designed to support early stages of embryonic growth (up to three days post-fertilization). P-1 has been formulated without glucose and phosphate, which may be detrimental to blastocyst development. P-1 may be used as a stand-alone medium, or as the first stage of a sequential medium protocol.
Here's an analysis of the acceptance criteria and study information for the P-1® (Preimplantation Stage One) Medium, based on the provided text:
Device: P-1® (Preimplantation Stage One) Medium
Study Goal: To demonstrate that P-1® medium is suitable for its intended use (supporting early stages of embryonic growth) and meets the criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335.
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| I. Functional for intended use (support of embryonic growth) | P-1® is assayed by mouse embryo assay prior to release to market, which "assures that the product is both functional for its intended use, the support of embryonic growth." |
| II. Absence of toxic components in the formulation | P-1® is assayed by mouse embryo assay prior to release to market, which "assures that... no toxic components are present in the formulation." Additionally, endotoxin and sterility testing will be performed as a condition of release. |
| III. Compliance with Notice of Final Rule, 63 FR 48428, Docket number 97N-0335 | "The conclusion from performance testing, as well as a review of the historical information contained in professional literature shows that P-1 is suitable for its intended use, and meet the criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335." |
Study Details
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Sample size used for the test set and the data provenance:
- Mouse Embryo Assay: The text states, "P-1 is assayed by mouse embryo assay prior to release to market." This indicates a prospective testing protocol for each lot produced. The specific sample size for a typical mouse embryo assay (e.g., number of embryos, number of replicates) is not specified in the document.
- Clinical Settings: "P-1 has been used in a variety of clinical settings, for its intended use, for a number of years. In that time, the product has become the standard media used for the early development of human embryos in vitro." This suggests a large, retrospective collection of real-world usage data. No specific sample size (e.g., number of patients, number of cycles, number of embryos) is provided for this historical data, nor is a specific country of origin mentioned for these "clinical settings."
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document implies that the mouse embryo assay serves as the primary method for establishing the functional integrity and non-toxicity of each lot. The "experts" involved in conducting and interpreting these assays are not explicitly quantified or qualified. However, standard laboratory practices for such assays would typically involve trained embryologists or laboratory technicians.
- For the "historical information contained in professional literature" and the device becoming "the standard media," this would rely on the collective expertise of the assisted reproductive technology (ART) community, but no specific number or qualifications of experts are cited as being part of this specific submission's ground truth establishment.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- The document does not describe an adjudication method for the mouse embryo assay results or the review of historical clinical use. For a standard laboratory assay, internal quality control and interpretation by trained personnel would be the norm, but a formal adjudication process (like 2+1) is not indicated.
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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:
- No MRMC study was performed. This device is a culture medium, not an imaging or diagnostic device requiring human interpretation, nor does it involve AI assistance. Therefore, this type of study is irrelevant to this submission.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This question is not applicable as the device is a culture medium and does not involve an algorithm or human-in-the-loop performance in the way a diagnostic software would. The "performance" is the biological outcome of supporting embryo development, which is observed directly, not through an algorithm.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Mouse Embryo Assay: This involves direct observation of biological outcomes (embryonic development and viability) in a controlled animal model, serving as a proxy for human embryo development. The "ground truth" here is the observed developmental stage and absence of toxicity in the mouse embryos.
- Historical Clinical Use: This relies on human clinical outcomes data from actual assisted reproductive procedures, observed over time by clinicians and embryologists, implicitly leading to the consensus that it has become a "standard media."
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The sample size for the training set:
- This concept is not applicable to this device. As a biological culture medium, there is no "training set" in the context of machine learning or algorithm development. The "training" in a biological sense would be the extensive research and development that led to the P-1 formulation, but this isn't analogous to a training set for an AI model.
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How the ground truth for the training set was established:
- As there is no "training set" for an algorithm, this question is not applicable. The development of the medium's formulation would have been based on established scientific principles of embryology and cell culture, empirical testing, and historical knowledge of nutrient requirements for embryo development.
§ 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.