(252 days)
The INVOcell Culture Device is indicated for use in preparing, holding, and transferring human gametes or embryos during In Vitro Fertilization/Intra Vaginal Culture (IVF/IVC) and Intra-cytoplasmic Sperm Injection Fertilization/Intravaginal Culture (ICSI/IVC) procedures. The INVOcell Culture Device is indicated for use with the INVOcell Retention Device and the INVOcell Holding Block. The INVOcell Culture Device is not indicated for incubation periods exceeding 72h.
The INVOcell Retention Device is indicated for use with the INVOcell Culture Device to aid in retention of the INVOcell Culture Device in the vaginal cavity during the incubation period. The INVOcell Retention Device is not indicated for use exceeding 72 hours.
The INVOcell Holding Block is indicated for use with the INVOcell Culture Device to aid in temperature maintenance of the INVOcell Culture Device during loading and collection procedures and to aid in positioning and observation of the INVOcell Culture Device during human gamete/embryo loading and collection procedures.
The INVOcell Intravaginal Culture System is comprised of three parts: the INVOcell Intravaginal Culture Device, the INVOcell Retention Device, and the INVOcell Holding Block. All devices are designed to be utilized together.
INVOcell Intravaginal Culture Device: a single-use plastic container that serves to house and protect the gametes and/or embryos during intravaginal culture. It is provided sterile. The culture device consists of two components: the inner chamber and the outer shell.
INVOcell Retention Device: aids in the retention of the INVOcell Intravaginal Culture Device during incubation in the vagina. It is a single-use device that is provided nonsterile. The device is a cup-shaped silicone piece that includes to allow flow of vaginal secretions. The device comes in four sizes (65, 70, 75, and 80 mm). It is accompanied by a fitting kit, which is utilized to determine the appropriate diameter of the INVOcell Retention Device to ensure appropriate retention, and is intended to be reprocessed.
INVOcell Holding Block: designed to hold and maintain temperature of the inner vessel of the INVOcell Intravaginal Culture Device during loading and retrieval procedures. The block does this passively by serving as a heat sink. Prior to use, the block is preheated to body temperature. The block then can be utilized to hold the Intravaginal Culture Device inner vessel, and will maintain appropriate temperature for short periods of time. The block is solid stainless steel, with a conical hole in the top for the inner vessel. The block also includes a glass window on the side, to allow viewing of the embryos in the inner vessel during retrieval.
Here's an analysis of the acceptance criteria and the studies that prove the device meets them, based on the provided text:
Key Takeaways:
- Device: INVOcell Intravaginal Culture System, comprising the INVOcell Culture Device, INVOcell Retention Device, and INVOcell Holding Block.
- Purpose: Intended for preparing, holding, and transferring human gametes or embryos during intravaginal in vitro fertilization (IVF) or intravaginal culture (IVC) procedures.
- Approval Basis: FDA De Novo classification. This means there was no existing predicate device, so the manufacturer had to demonstrate safety and effectiveness.
- Study Types: Primarily non-clinical bench studies and two clinical studies.
1. Table of Acceptance Criteria and Reported Device Performance
The provided text has an excellent table summarizing the non-clinical/bench studies, their purpose, methods, acceptance criteria, and results. I will reproduce key parts of that table and also synthesize clinical performance criteria from the "Special Controls" section.
Acceptance Criteria and Reported Device Performance for INVOcell Intravaginal Culture System
Test Category | Specific Test | Acceptance Criteria | Reported Device Performance and Results |
---|---|---|---|
Non-Clinical/Bench Studies | |||
Sterilization, Cleaning, Disinfection | Sterilization (Culture Device) | Sterility Assurance Level (SAL) shall be 10^-6 | Passed |
Reprocessing (Holding Block) | >6-log10 reduction in microorganism counts | Passed | |
Biocompatibility | Cytotoxicity | Not explicitly stated (implied: non-cytotoxic) | Grade 0 (non-cytotoxic) |
Rabbit Muscle Implantation | Not explicitly stated (implied: no significant toxic effects) | No significant difference from negative control (no signs of toxic response) | |
Vaginal Irritation | Not explicitly stated (implied: no irritation) | No signs of macroscopic or microscopic irritation from polar and non-polar extracts | |
Sensitization | Not explicitly stated (implied: no sensitization) | No signs of sensitization from polar and non-polar extracts | |
Acute Systemic Toxicity | Not explicitly stated (implied: no systemic toxicity) | No evidence of mortality or systemic toxicity from test material extracts | |
Bench Testing | Volumetric Capacity | Inner vessel volume shall meet specification, and no bubbles or air pockets shall be formed during filling | Passed. No bubbles or air pockets were observed. |
Fluid Contact Surface Finish | No surface imperfections ≥ 50 microns shall be observed | Passed | |
Illumination and Optical Properties | Not explicitly stated (implied: ability to observe embryos) | No obscured views, 89% of samples scored 5/5, 11% were 4/5. | |
Temperature Maintenance | Media inside inner vessel shall maintain a temperature of >34°C for >10 minutes | Passed; Block maintains temperature of inner vessel (>34°C) for 12 minutes. | |
pH Maintenance | pH shall remain within ±0.2 of controls (legally marketed ART labware) | Passed | |
Seal Integrity | Culture media within the inner vessel shall remain sterile during incubation and extraction | Passed; 30/30 samples maintained culture media sterility during incubation and extraction. | |
Mouse Embryo Assay (Embryo compat.) | >80% embryos shall reach expanded blastocyst stage | Passed; >90% of embryos reached expanded blastocyst stage. | |
Endotoxin Testing | The endotoxin level shall be 80% of embryos shall reach the blastocyst stage | Passed, >90% reached blastocyst stage. | |
pH maintenance (end of shelf) | pH shall remain within ±0.2 of the control | Passed | |
Clarity of vessel wall (end of shelf) | Ability to identify and count embryos accurately | Passed | |
Seal integrity (end of shelf) | Culture media within the inner vessel shall remain sterile during incubation and extraction (worst-case scenario) | Passed; 30/30 samples maintained culture media sterility during incubation and extraction. | |
Clinical Performance Testing (from Special Controls) | |||
Performance Characteristics | Comfort and retention of device | Demonstrated retention and minimal discomfort (implied based on study results) | Study 2: Retention for 72hr in 25/29 subjects (100% with Retention Device). Majority reported minimal discomfort. |
Adverse vaginal tissue reactions | Demonstrated absence of significant reactions (implied based on study results) | Study 2: No reports of erythema, ulceration, or lesions. | |
Maximum number of gametes/embryos | Indicated for up to 7 oocytes/embryos (based on clinical data supporting this limit) | Majority of clinical data |
§ 884.6165 Intravaginal culture system.
(a)
Identification. An intravaginal culture system is a prescription device intended for preparing, holding, and transferring human gametes or embryos during intravaginal in vitro fertilization or intravaginal culture procedures.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing must demonstrate the following:
(i) Comfort and retention of the intravaginal culture device;
(ii) Adverse vaginal tissue reactions associated with intravaginal culture;
(iii) Maximum number of gametes and/or embryos that can be placed in a device; and
(iv) Rates of embryo development to the designated stage, implantation rates, clinical pregnancy rates, live birth rates, and any adverse events or outcomes.
(2) Nonclinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be demonstrated:
(i) Mouse embryo assay testing to assess embryotoxicity by evaluating the gamete and embryo-contacting device components effect on the growth and development of mouse embryos to the blastocyst stage;
(ii) Endotoxin testing on gamete and embryo-contacting components of the device;
(iii) Cleaning and disinfection validation of reusable device components;
(iv) Sterility maintenance of the culture media within the device throughout the vaginal incubation period and subsequent embryo extraction; and
(v) Ability of the device to permit oxygen and carbon dioxide exchange between the media contained within the device and the external environment throughout the vaginal incubation period.
(3) The patient-contacting components of the device must be demonstrated to be biocompatible.
(4) Performance data must demonstrate the sterility of the device components intended to be provided sterile.
(5) Shelf life testing must demonstrate that the device maintains its performance characteristics and the packaging of device components labeled as sterile maintain integrity and sterility for the duration of the shelf life.
(6) Labeling for the device must include:
(i) A detailed summary of the clinical testing, including device effectiveness, device-related complications, and adverse events;
(ii) Validated methods and instructions for reprocessing of reusable components;
(iii) The maximum number of gametes or embryos that can be loaded into the device;
(iv) A warning that informs users that the embryo development is first evaluated following intravaginal culture; and
(v) A statement that instructs the user to use legally marketed assisted reproductive technology media that contain elements to mitigate the contamination risk (
e.g., antibiotics) and to support continued embryonic development over the intravaginal culture period.(7) Patient labeling must be provided and must include:
(i) Relevant warnings, precautions, and adverse effects and complications;
(ii) Information on how to use the device;
(iii) The risks and benefits associated with the use of the device; and
(iv) A summary of the principal clinical device effectiveness results.