(90 days)
Dewin Gamete Buffer is intended for human gamete and embryo short-term handling procedures outside the incubator, including washing and intracytoplasmic sperm injection (ICSI).
Dewin Follicle Flushing Solution is intended for use during ovarian follicle flushing and oocyte collection procedures for use in in vitro fertilization procedures.
Dewin One Step Medium is intended for use for culture of embryos from fertilization to the blastocyst stage. This device can be used for transfer of embryos to the uterus.
The DonneVie Dewin Reproductive Media are solutions used in assisted reproductive procedures. The family of Reproductive Media include the following 3 types and their variants:
- Dewin Gamete Buffer [with and without Human Serum Albumin (HSA)];
- Dewin Follicle Flushing Solution;
- Dewin One Step Medium [with and without HSA].
All variants contain gentamicin, an antibiotic agent that suppresses bacterial growth. The Gamete Buffer and Follicle Flushing media are offered in 100mL volume, while the One Step Medium is offered in volumes of 25mL and 50mL. The three Dewin Reproductive Media are used together during an assisted reproductive procedure. The Follicle Flushing Solution is used to first flush/wash the Cumulus-Oocyte Complex after it's removed from the ovary; it is then transferred to the Gamete Buffer for cleaning. After the prepared oocyte has been fertilized, it is transferred to the One Step Medium to culture the embryo from fertilization to blastocyst stage.
The primary glass bottle containers are washed, then sterilized and depyrogenated via dry heat. The bottle caps are supplied sterile by electron beam irradiation. The media are sterile filtered through a 0.2µm filter in an aseptic isolator at DonneVie Medical Technology Co., Ltd.
The provided FDA 510(k) clearance letter describes a medical device called "Dewin Reproductive Media" and presents non-clinical performance testing to demonstrate its substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Dewin Reproductive Media are primarily derived from the specifications compared to the predicate device and the results expected from specific non-clinical tests.
| Acceptance Criteria Category | Specific Acceptance Criteria | Reported Device Performance | Comments |
|---|---|---|---|
| Appearance | Clear, particulate free | Met after real-time aging (Shelf-life testing) | Confirmed through visual inspection as part of shelf-life testing. |
| pH (per USP ) | 7.2 - 7.5 | Met after real-time aging (Shelf-life testing) | Within the specified range after aging. |
| Osmolality (per USP ) | 260 - 295 mOsm/kg | Met after real-time aging (Shelf-life testing) | Within the specified range after aging. |
| Endotoxin (per USP ) | )** | No microbial growth | Met after real-time aging (Shelf-life testing) |
| Mouse Embryo Assay (MEA) for Dewin One Step Medium | ≥ 80% embryos developed to expanded blastocyst at 120 hours | Met after real-time aging (Shelf-life testing) | Demonstrated equivalent or better performance than predicate specifications. |
| Mouse Embryo Assay (MEA) for Dewin Gamete Buffer | ≥ 80% developed to expanded blastocyst at 96 hours after 30 min exposure | Met after real-time aging (Shelf-life testing) | Demonstrated equivalent or better performance than predicate specifications. |
| Mouse Embryo Assay (MEA) for Dewin Follicle Flushing Solution | ≥ 80% embryos developed to expanded blastocyst at 96 hours after 30 min exposure | Met after real-time aging (Shelf-life testing) | Demonstrated equivalent or better performance than predicate specifications. |
| Sterilization Process (Aseptic Filtration) | Aseptic filtration validated per ISO 13408-1:2008 & A1:2013 and ISO 13408-2:2018. | Validated, with filter challenge test using worst-case conditions (excluding antimicrobials). | Ensures sterility of the media. |
| Sterilization Process (Glass Bottles) | Dry heat sterilization per 20857:2010/(R)2015. | Validated. | Ensures sterility of the primary packaging. |
| Sterilization Process (Bottle Caps) | Radiation sterilization per ISO 11137-1:2006 and ISO 11137-2:2013. | Validated. | Ensures sterility of the bottle closures. |
| Shelf-life | Gamete Buffer: 7 months; Follicle Flushing Solution: 12 months; One Step Medium: 4 months. | Met for respective products (Shelf-life testing) | Performance maintained for the specified duration. |
| Transportation Testing | Resistance to transportation stresses per ASTM D4169-22. | Performed. | Ensures product integrity during shipping. |
| Cap/Seal Leak Testing | Method equivalent to USP on transportation-conditioned devices. | Performed. | Ensures product integrity and sterility is maintained. |
| Biocompatibility (Dewin Follicle Flushing Solution & Dewin One Step Medium) | Cytotoxicity (ISO 10993-5:2009); Guinea Pig Maximization Sensitization Test (ISO 10993-10:2021); Intracutaneous Reactivity (ISO 10993-23:2021). | Results support biocompatibility. | Confirmed safety for patient contact. |
2. Sample Size Used for the Test Set and the Data Provenance
The document does not specify the exact sample sizes for most of the non-clinical tests conducted. For example, it doesn't state how many batches were tested for sterility, pH, osmolality, or endotoxin, nor does it specify the number of mouse embryos used in the MEA tests.
- Provenance: The studies were conducted by DonneVie Medical Technology (Shanghai) Co. Ltd. This implies the data provenance is likely from China, as that is the submitter's location. The studies are non-clinical, meaning they are laboratory tests, not human trials. They are implicitly prospective in the sense that they were designed and executed to test the device's performance against predefined criteria.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This section is not applicable as the studies described are non-clinical laboratory tests, not studies requiring expert interpretation of medical images or patient outcomes. The "ground truth" for these tests (e.g., pH value, osmolality, microorganism presence, blastocyst development) is established through established laboratory methods and validated instrumentation, not by expert consensus in a clinical diagnostic context.
4. Adjudication Method for the Test Set
This section is not applicable. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies, particularly in cases where human readers or diagnosticians are involved and their interpretations need to be reconciled to establish a ground truth. For laboratory tests, the results are typically quantitative or qualitative outcomes determined by a predefined method, eliminating the need for expert adjudication in this typical sense.
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
This section is not applicable. The device is a "Reproductive Media," which are solutions used in assisted reproductive procedures (e.g., for washing gametes, culturing embryos). It is not an AI-powered diagnostic device or an imaging system. Therefore, no MRMC study involving human readers or AI assistance would be relevant or conducted for this type of product.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
This section is not applicable. The device is a reproductive media solution, not an algorithm or an AI system. Its performance is evaluated through physical, chemical, and biological laboratory tests, not through algorithmic output.
7. The Type of Ground Truth Used
The ground truth for the non-clinical tests is established through:
- Physicochemical Measurements: For parameters like pH, osmolality, and endotoxin, the ground truth is the numerical value obtained using validated analytical instruments and methods (e.g., pH meter, osmometer, LAL assay).
- Biological Endpoints: For the Mouse Embryo Assay (MEA), the ground truth is the observed development of mouse embryos to the expanded blastocyst stage within a specified timeframe, as assessed under a microscope by trained personnel following a standardized protocol.
- Microbiological Endpoints: For sterility testing, the ground truth is the absence of microbial growth in culture, determined by standard microbiological techniques.
- Regulatory Standards: Compliance with ISO standards for sterilization, biocompatibility, and transportation testing.
8. The Sample Size for the Training Set
This section is not applicable. The Dewin Reproductive Media is a chemical/biological product, not a machine learning model or AI system that requires a "training set." The product's formulation and manufacturing processes are developed through research and development, not by training an algorithm on a dataset.
9. How the Ground Truth for the Training Set was Established
This section is not applicable as there is no "training set" for this type of device.
§ 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.