(192 days)
Serum Substitute Supplement is intended for use in assisted reproductive procedures that require protein supplementation. These procedures include in vitro fertilization, embryo culture and growth, and embryo cryopreservation.
Serum Substitute Supplement (SSS) is designed for those assisted reproductive procedures that require the use of a protein supplement. In particular, SSS is intended for use during in vitro fertilization, during in vitro embryo culture to the desired stage of embryo development, and for the cryopreservation of human embryos.
Serum Substitute Supplement consists of human serum albumin from therapeutic-grade source material (5mg/mL) and human serum globulins (1mg/mL) in a sterile saline solution.
Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the Serum Substitute Supplement (SSS) device:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Explicit or Implied) | Reported Device Performance |
|---|---|
| Functionality for intended use: Support of embryonic growth (in vitro fertilization, embryo culture, cryopreservation) | "Assures that the product is both functional for its intended use, the support of embryonic growth." |
| "Used in a variety of clinical settings... for a number of years... has become one of the standard protein supplements used for the in vitro fertilization, growth and cryopreservation of human gametes and embryos." | |
| Absence of toxic components: Non-toxic formulation | "Assures... that no toxic components are present in the formulation." |
| Sterility: Product is sterile | Sterility testing performed as a condition of release. |
| Endotoxin Content: Endotoxin levels within acceptable limits | Endotoxin testing performed as a condition of release. |
| Historical Performance/Clinical Acceptance: Established use and acceptance in clinical settings | "Used in a variety of clinical settings, for its intended use, for a number of years. In that time, the product has become one of the standard protein supplements..." |
| Compliance with regulatory standards: Meets criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335 | "Meets the criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335." |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: Not explicitly stated in terms of a numerical count of embryos or cases. The primary test mentioned is the "mouse embryo assay."
- Data Provenance:
- Mouse embryo assay: Implied to be lab-based, likely controlled experiments.
- "Variety of clinical settings": This suggests retrospective observation or long-term clinical experience, but specific study design (e.g., retrospective vs. prospective) is not detailed. The phrase "for a number of years" reinforces a historical, rather than a single prospective study.
- Country of Origin: Not specified, but given the submission is to the US FDA, it's presumed to be relevant to US regulatory standards, though the clinical settings where it was used are not geographically identified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- The document does not detail the use of "experts" in the traditional sense for establishing ground truth for a test set.
- The "mouse embryo assay" implies standard biological protocols and evaluation by trained lab personnel, but not a panel of clinical experts for ground truth.
- The "variety of clinical settings" suggests that clinical embryologists and reproductive medicine specialists have used and evaluated the product over time, implicitly forming a consensus on its effectiveness, but a formal "ground truth" establishment process by a specific number of qualified experts is not described.
4. Adjudication Method for the Test Set
- No formal adjudication method (like 2+1, 3+1) is mentioned. The mouse embryo assay likely relies on objective biological endpoints (e.g., embryo development rates). The "clinical settings" aspect implies real-world outcomes that are evaluated by the treating physicians, but not via an independent adjudication panel for a specific test set.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
- No MRMC comparative effectiveness study was mentioned. This device is a biological supplement, not an AI or diagnostic imaging device that would typically involve human readers. Therefore, there's no discussion of human reader improvement with or without AI.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Not applicable. This device is a serum substitute supplement, not a standalone algorithm. Its performance is intrinsic to its biological function rather than an automated analysis.
7. The Type of Ground Truth Used
- Mouse Embryo Assay: The ground truth for this assay is likely based on established biological criteria for successful embryo development (e.g., grading of blastocyst formation, cell numbers, viability) as observable biological outcomes.
- Clinical Settings: For the human applications, the ground truth is based on outcomes data and expert consensus within the clinical reproductive medicine community. This includes successful in vitro fertilization, embryo culture to desired stages, and effective cryopreservation as observed through clinical practice. The statement that it "has become one of the standard protein supplements" implies a strong, widely accepted clinical ground truth.
8. The Sample Size for the Training Set
- Not applicable. The device is a biological supplement, not a machine learning model, so there is no concept of a "training set" for an algorithm. The development of the formulation and prior clinical experience could be considered analogous to a "training" period for understanding product efficacy, but not in the context of an AI model.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. As stated above, there is no training set in the context of an AI device. The product's development and optimization would rely on standard laboratory research and preclinical testing to establish its biological properties and efficacy.
§ 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.