(54 days)
Multipurpose Handling Medium™ (MHM™) is intended for use in assisted reproductive procedures which involve the manipulation of gametes or embryos. Specifically, Multipurpose Handling Medium™) is indicated for use as an oocyte retrieval medium during ovarian follicle aspiration procedures (not for flushing ovarian follicles), washing sperm prior to IVF and ICSI fertilization procedures, and for transport of the embryo to the uterus during embryo transfer procedures.
The Multipurpose Handling Medium™ (MHM™) is based upon the mHTF (K983586) formulation. The formula for the Multipurpose Handling Medium™ (MHM™) is based upon the composition of modified HTF, K983586. The medium uses a buffering system composed of HEPES (N-2-Hydroxyethylpiperazine-N1 - - 2 - - ethanesulfonic acid). MOPS . (3 Morpholinopropane - 1- sulfonic acid) and Sodium Bicarbonate. This buffering system provides pH maintenance over the physiologic range and does not require the use of a CO2 Incubator. - The product also contains 10 ug/mL gentamicin.
Multipurpose Handling Medium™ (MHM™) has utility as an oocyte retrieval medium, in procedures that aspirate oocytes from the patient's ovarian follicles. Multipurpose Handling Medium™ (MHM™) is used only in the oocyte collection vessel and is not for use in flushing oocytes from ovarian follicles. Once the oocyte has been retrieved, it is placed into a culture dish with an appropriate amount of a culture medium (does not include MHM™), as specified by the user's internal procedures, and fertilization is allowed to occur. Multipurpose Handling Medium™ (MHM™) can also be used to wash sperm in preparation for fertilization by conventional IVF or ICSI procedures. The fertilized oocyte (zygote) is allowed to grow in the culture dish, supported by a culture medium (does not include MHM™), as specified by the user's internal procedures, and an appropriate protein supplement, in a carbon dioxide incubator at 37°C until the desired stage of development is achieved. The embryo is removed from the culture dish, placed into an appropriate amount of Multipurpose Handling Medium™ (MHM™) for transfer into the uterus.
Multipurpose Handling Medium™ (MHM™) is supplied as a ready to use liquid, in 100 and 500 mL bottles.
Here's a breakdown of the acceptance criteria and the study details for the Multipurpose Handling Medium™ (MHM™) device, based on the provided text:
Acceptance Criteria and Device Performance
| Specification | Acceptance Criteria for MHM™ | Reported Device Performance |
|---|---|---|
| pH | 7.25 - 7.54 | 7.25 - 7.54 (Matching Predicate) |
| Osmolality | 275 - 295 Osm/KgH2O | 275 - 295 Osm/KgH2O |
| Sterility | Pass | Pass |
| Endotoxin | ≤ 0.25 EU/mL | ≤ 0.25 EU/mL |
| Mouse Embryo Assay (MEA) | ≥ 80% | ≥ 80% |
| Human Sperm Survival Assay (HSSA) | ≥ 70% of original motility at 24 hours | ≥ 70% of original motility at 24 hours (Equal to control mHTF) |
Study Details
1. Sample Sizes and Data Provenance
- Test Set (MEAs): The MEA testing was performed at three (3) different test facilities. The document does not specify the number of individual embryos or mouse embryos used per test, nor the country of origin of the data. The data is retrospective as it was performed as part of design validation prior to release.
- Test Set (HSSA): The HSSA was performed on donor specimens. The number of donor specimens is not specified. The data is retrospective as it was performed prior to release. The document does not specify the country of origin.
- Training Set: The sample size for the training set is not explicitly stated. This is likely because the MHM™ is a medium and its "training" or formulation development would involve biochemical and cell culture experiments rather than machine learning on a dataset in the traditional sense. The formulation is based on existing, predicate devices (mHTF and G-MOPS™/G-MOPS™ PLUS).
2. Number of Experts and Qualifications for Ground Truth (Test Set)
- The document does not explicitly state the number of experts used to establish the ground truth for the test set or their qualifications. For MEAs and HSSAs, the "ground truth" is typically the quantitative results of the assay (e.g., percentage of embryos reaching a certain stage, percentage of motile sperm), which are objectively measured by laboratory personnel, rather than through expert consensus on qualitative observations.
3. Adjudication Method for the Test Set
- The document does not mention an adjudication method. For quantitative assays like MEAs and HSSAs, adjudication is generally not applicable in the same way it would be for qualitative assessments (e.g., image interpretation). The results are based on objective measurement.
4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not conducted. This type of study is typically relevant for medical devices that involve human interpretation (e.g., diagnostic imaging AI). The MHM™ is a cell culture medium, and its performance is evaluated through biological assays.
5. Standalone Performance (Algorithm Only)
- Yes, standalone performance was done in the sense that the medium itself (the "device") was tested directly in the described assays (MEA, HSSA) without human intervention in the assay's outcome interpretation beyond standard laboratory procedures. There is no "algorithm" in the traditional sense for this device; its performance is intrinsic to its chemical composition and how it supports biological processes.
6. Type of Ground Truth Used
- Mouse Embryo Assay (MEA): The ground truth is established by the biological outcome of the assay, specifically the percentage of one-cell mouse embryos that develop to a specific stage (not explicitly stated, but typically blastocyst stage, or viability at 24/48/72 hours) after exposure to the medium. This is a direct measure of embryo toxicity/support.
- Human Sperm Survival Assay (HSSA): The ground truth is the percentage of motile human sperm after 24 hours at 37°C in ambient air, following exposure to the medium. This directly assesses sperm viability and function.
7. Sample Size for the Training Set
- As noted above, the sample size for a "training set" in the context of this biological medium is not applicable or explicitly stated in the document. The formulation was based upon existing predicate devices (mHTF and G-MOPS™/G-MOPS™ PLUS), implying an iterative development process informed by previous research and established formulations.
8. How Ground Truth for the Training Set Was Established
- The ground truth for the development of the MHM™ (the "training" equivalent) would have been established through pre-clinical research and development experiments focused on optimizing the medium's composition to support gamete and embryo viability and function. This includes:
- Literature review and knowledge of existing formulations: The MHM™ is "based upon" the mHTF formulation, which itself has established efficacy.
- Benchtop biochemical analysis: Measuring pH, osmolality, and sterility, and ensuring non-toxic component levels.
- Pilot biological assays: Performing MEAs, HSSAs, and potentially other cell culture tests on various prototype formulations to identify those that yield optimal biological outcomes.
- The document specifically mentions that MHM™ is assayed by MEA and HSSA prior to release, which serves as a final validation step to ensure consistency, not necessarily the ground truth establishment for training the initial formulation.
§ 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.