(121 days)
The micropipet family's intended use is to manipulate zygotes during the ICSI procedure.
The micropipets are used in the tissue culture techniques performed by embryologists when injecting a single sperm into an egg, or assisting an embryo in hatching prior to reimplantation.
The micropipets are tools used in procedures that have been developed to aid infertile couples achieve pregnancy. Specifically, the ICSI procedure is beneficial in cases where the male fertility is impaired.
Micropipets are fabricated from 1 mm. diameter borosilicate glass capillary tubes. One end of the glass tube is pulled to a much smaller diameter using a glass puller with a heated coil. Diameters range from 2 - 3 um to 200 um depending upon the type of micropipet. Most micropipets are ground on a microgrinder to produce a beveled or flat opening. Generally, a sharp spike is pulled on beveled micropipets by touching the bevel to a heated glass bead and withdrawing quickly. Angles may be added along the shaft of the micropipet per request of the end user to best fit their micromanipulation equipment. Specifications for each variation of micropipet is as follows:
Intracytoplasmic Sperm Injection Micropipets (ICSI) - pulled to a 6 to 7 um outer diameter, 4 to 5 um inner diameter with a 35 or 50 degree bevel and a short, sharp point or may be made with no point. May be straight or with an angle (15 - 45 degrees as specified), 0.5mm from the beveled end. Any of these parameters may be modified to meet customer specifications.
Spermatid ICSI Micropipets - pulled to a 9 um outer diameter, 7 to 8 um inner diameter with a 35 or 50 degree bevel and a short, sharp point at the tip. May be straight or with an angle (15 to 45 degrees as specified), 0.5 mm from the beveled end. Again, parameters may vary somewhat depending on customer specifications.
Holding Micropipets - one end is pulled to the specified outer diameter, which can range from 65 um to 180 um, scored and cut to yield a blunt opening of the appropriate size, and polished over a hot glass bead to a 20 to 25 um inner diameter opening, unless otherwise specified. Small holding micropipets are pulled to an outer diameter of 65 to 95 um, medium holdings are pulled to an outer diameter of 100 to 120 um, large holdings are pulled to an outer diameter of 125 to 150 um, and extra large holding micropipets are pulled to an outer diameter of 155 to 180 um. Holding micropipets may be angled or straight.
Assisted Hatching Micropipets - one end is pulled to a standard outer diameter of 8 to 10 um unless otherwise specified, with a blunt opening. Other outer diameter sizes are available upon request. Assisted hatching micropipets may be straight or angled (15 to 45 degrees as specified), 0.5 mm from the tapered end.
Subzonal Insertion Micropipets (SUZI) - one end is pulled to a 10 to 12 um outer diameter with a 40 degree bevel, and a short, sharp point at the tip. SUZI micropipets may be straight or angled (15 to 45 degrees as specified), 0.5 mm from the tapered end.
Partial Zona Dissection Micropipets (PZD) - one end is pulled to a long, thin taper with a closed, sharp point. PZD micropipets may be straight or angled (15 to 45 degrees as specified), 0.5 mm from the tapered end.
Denuding Micropipets - one end is pulled and then cut with a diamond knife to an opening of 150 or 190 um inner diameter with a blunt opening.
The provided text describes the acceptance criteria and study for the Humagen Fertility Diagnostics, Inc. micropipets.
1. Table of Acceptance Criteria and Reported Device Performance
| Test Type | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Mouse Embryo Bioassay (Toxicity) | Non-toxic if the combined percent of embryos developing to expanded and/or hatching blastocysts in the treated group is within 10% of the control group, and no contamination of the culture has occurred. | The study implies that the device met these criteria, as the information is presented as a description of how performance is assessed for acceptability. The exact performance percentage for treated vs. control is not given, but acceptance is implied. |
| Sterilization (Sterility Assurance Level - SAL) | 10⁻⁶ SAL | Achieved 10⁻⁶ SAL |
| Minimum Radiation Dose for Sterilization | 21.8 kGy (established by AAMI Method 1, SIP) | Minimum established radiation dose is 21.8 kGy |
| Maximum Radiation Dose for Sterilization | 40 kGy (based on physical characteristics of materials) | Maximum limit of 40 kGy |
| Endotoxin Levels | Less than 20 endotoxin units per device | The study implies that the device met this criterion, as the information is presented as a description of how performance is assessed for acceptability. The exact endotoxin level is not given, but acceptance is implied. |
2. Sample size used for the test set and the data provenance
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Sample Size for Test Set:
- Mouse Embryo Bioassay: For the toxicity test, 25 µl tissue culture medium was used, and embryos were cultured starting at the two-cell stage. The number of embryos used in each group (treated and control) is not explicitly stated, but it would involve enough embryos to assess the "combined percent of embryos developing to expanded and/or hatching blastocysts."
- Sterilization: The "Methods" for determining the minimum established radiation dose (AAMI Method 1, SIP) would involve a sample size to achieve statistical confidence in the 10⁻⁶ SAL, but the specific number is not provided. Quarterly dose audits are conducted.
- Endotoxin: No specific sample size is provided, but each lot of micropipets is tested.
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Data Provenance: The data is generated from in vitro laboratory testing of the device itself (mouse embryo bioassay, sterilization validation, endotoxin testing). There is no mention of human clinical data, retrospective, or prospective studies in this context. The testing is described as internal quality control and validation for the specific device.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Mouse Embryo Bioassay: The interpretation of mouse embryo development (expanded and/or hatching blastocysts) would typically be performed by trained embryologists or laboratory personnel experienced in bioassays. The document does not specify the number or qualifications of experts involved in assessing the mouse embryo results.
- Sterilization and Endotoxin Testing: These tests are objective laboratory assays. The "ground truth" is established by the specified chemical and biological measurement methods (e.g., AAMI Method 1 for sterility, Limulus Amebocyte Lysate assay for endotoxin). While experts design and oversee these tests, the ground truth is derived directly from the assay results against predefined criteria, not from expert consensus on subjective observations. The document mentions an "outside testing laboratory" for quarterly dose audits, implying involvement of qualified personnel from that lab.
4. Adjudication method for the test set
- Mouse Embryo Bioassay: The criteria for non-toxicity are objective: "within 10% of the control group, and no contamination." If multiple individuals assess the embryos, their readings would need to align with these objective criteria. No specific adjudication method (e.g., 2+1, 3+1) is mentioned, suggesting direct application of the criteria.
- Sterilization and Endotoxin Testing: These are objective laboratory tests with predefined cut-offs. Adjudication is not typically needed in the sense of reconciling different expert opinions; rather, the results are compared directly to the numerical acceptance criteria.
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
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This document describes a medical device (micropipets) that is a tool, not an AI or diagnostic imaging system. Therefore, the concept of "human readers" and "AI assistance" as typically applied in MRMC studies is not relevant here.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- No, a standalone algorithm performance study was not conducted. This device is a physical tool used by embryologists. It does not involve a software algorithm or AI operating in a standalone mode.
7. The type of ground truth used
- Mouse Embryo Bioassay (Toxicity): The ground truth for toxicity is based on biological outcomes data (embryo development to expanded and/or hatching blastocysts in treated vs. control groups).
- Sterilization and Endotoxin Levels: The ground truth for sterility and endotoxin levels is based on objective biological/chemical assay results (e.g., bacterial growth, Limulus Amebocyte Lysate reaction) compared against predefined scientific/regulatory standards.
8. The sample size for the training set
- There is no mention of a "training set" in the context of this device. The described testing procedures are for quality control and validation of manufacturing lots, not for training a machine learning model.
9. How the ground truth for the training set was established
- Not applicable, as there is no training set for a machine learning model described for this device.
§ 884.6130 Assisted reproduction microtools.
(a)
Identification. Assisted reproduction microtools are pipettes or other devices used in the laboratory to denude, micromanipulate, hold, or transfer human gametes or embryos for assisted hatching, intracytoplasmic sperm injection (ICSI), or other assisted reproduction methods.(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, and clinical testing). The device, when the assisted reproduction microtools (pipettes) are manufactured from glass, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.