(391 days)
"Medi-Cult Embryo Freezing Medium" is for freezing of early (2-8 cell stage) embryos.
"Medi-Cult Embryo Freezing Medium" is to be used with cryoprotectants for freezing and thawing of embryos. It is a phosphate buffered salt solution containing Assisted Reproduction Technique Supplement (ARTS) and Human Serum Albumin (HSA).
Here's an analysis of the provided text regarding the acceptance criteria and supporting studies for the "Medi-Cult Embryo Freezing Medium" device:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly define specific numerical acceptance criteria for the device's performance. Instead, it relies on demonstrating that the device performs comparably to or better than a national average or other established clinical outcomes.
| Acceptance Criteria (Implicit) | Reported Device Performance (Summary) |
|---|---|
| High Pregnancy Rate | Trondheim, Norway (1988-1998): 17.0% pregnancy rate per embryo replacement |
| Oslo, Norway (1994-1996): 18.3% pregnancy rate per embryo replacement | |
| (Compared to irrelevant national average for Norway, noted as not meaningful) | |
| High Birth Rate | Carl von Linne Clinic, Sweden (1997): 22% birth rate per frozen embryo replacement |
| UK Clinics using Medi-Cult (April 1996 - March 1997): Live birth rates ranging from 7.8% to 27.1% | |
| UK National Average (for comparison): 12.1% live birth rate per embryo replacement | |
| No Complaints/Adverse Events | "No registered complaints on the product and no evidence in the last 1.5 year that the product has been the cause of any serious adverse events." |
| User Satisfaction | "used extensively over a number of years to the satisfaction of the users at the IVF- and ART- clinics and laboratories." |
2. Sample Sizes Used for the Test Set and Data Provenance
The studies presented are retrospective clinical data from various IVF clinics.
- University of Trondheim, Norway:
- Sample Size (Test Set): 966 embryo replacements
- Data Provenance: Retrospective clinical data from Norway.
- The National Hospital, Oslo, Norway:
- Sample Size (Test Set): 465 embryo replacements
- Data Provenance: Retrospective clinical data from Norway.
- Carl von Linne Clinic, Sweden:
- Sample Size (Test Set): Not explicitly stated, but refers to "their birth rate per frozen embryo replacement."
- Data Provenance: Retrospective clinical data from Sweden.
- UK Clinics (Chelsea and Westminster, CARE at Park, Woking Nuffield, Leeds General Infirmary, Nurture, Holly House, Guy's and St Thomas):
- Sample Size (Test Set):
- Chelsea and Westminster Hospital: 24 FER-cycles
- CARE at Park Hospital: 95 FER-cycles
- The Woking Nuffield Hospital: 38 FER-cycles
- Leeds General Infirmary: 333 FER-cycles
- Nurture: 104 FER-cycles
- Holly House Fertility and IVF: 115 FER-cycles
- Guy's and St Thomas Assisted Conception Unit: 651 FER-cycles
- Total (sum of listed clinics): ~1360 FER-cycles
- Data Provenance: Retrospective clinical data from the UK, collected by the Human Fertilisation and Embryology Authority (HFEA).
- Sample Size (Test Set):
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The submission does not describe a process where explicit "experts" were used to establish a ground truth for a test set in the conventional sense of an AI/medical device study. The "ground truth" here is the actual clinical outcome (pregnancy or live birth) of IVF cycles, which are established through standard medical procedures and clinical records by the medical staff (doctors, embryologists, nurses) at the respective IVF clinics. No specific number or qualifications of these "experts" are provided, as they are inherent to the standard clinical practice where the data originated.
4. Adjudication Method for the Test Set
No adjudication method is described. The outcomes (clinical pregnancies, live births) are direct clinical results, not interpretations requiring adjudication by multiple parties.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The device is a culture medium, not an imaging or diagnostic device that involves human readers interpreting output. The studies compare the device's performance (clinical outcomes) against existing national averages or other clinics, not against human readers with and without AI assistance.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) Was Done
This question is not directly applicable. The device is a "freezing medium," not an algorithm. The studies assess the performance of the medium itself within the existing human-driven clinical process of IVF. There is no "algorithm only" performance to evaluate.
7. The Type of Ground Truth Used
The ground truth used in these studies is clinical outcomes data:
- Clinical pregnancies: Confirmed pregnancies.
- Live birth rates: Confirmed live births.
8. The Sample Size for the Training Set
The submission does not describe a separate "training set" in the context of an AI/machine learning model. The data presented are historical clinical outcomes used to demonstrate the device's acceptable performance, which could be considered analogous to validation data for a medical product. The product itself, being a medium, is not "trained."
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the context of a machine learning model for this device, this question is not applicable. The product's formulation is based on scientific research and data published in peer-reviewed journals, and its performance is demonstrated by the clinical outcome data mentioned in section 7.
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510(k) Summary Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination (K991472)
The product:
"Medi-Cult Embryo Freezing Medium" Cat. No. 1079
Indication for use:
Indication for use.
"Medi-Cult Embryo Freezing Medium" is for freezing of early (2-8 cell stage) embryos.
The medium has been specifically designed to meet the requirements of early (2-8 cell stage) embryos and freezing.
Product formulation:
Dulbecco's Phosphate Buffered Saline (PBS) supplemented with:
Assisted Reproduction Technique Supplement (ARTS) -
- Assisted Reproduction Treamigate Cappen a U.S licensed source (U.S license No.140).
"Medi-Cult Embryo Freezing Medium" is to be used with cryoprotectants for freezing and thawing of embryos. It is a phosphate buffered salt solution containing Assisted Reproduction Technique Supplement (ARTS) and Human Serum Albumin (HSA).
Product testing control contents:
- Bioburden, production-test -
- Integrity filter testing, production-test -
- Sterility, QC-test -
- pH, QC-test -
- Mouse Embryo, (two cells assay; ≥ 80% hatched), QC-test -
- Osmolarity, OC-test -
- Endotoxin, QC-test -
The Medi-Cult products for cryopreservation are in general formulated according to data published in peer reviewed international journals by internationally recognised scientists in the field. We have collected clinical data from clinics that use only products from Medi-Cult.
The clinical result of a given IVF-clinic will depend on the patient population treated, the clinical r no childer of the laboratory routines and on the various culture media used. A comparison of the clinical performance of clinics using only Medi-Cult media with other IVF-clinics using similar clinical and laboratory routines will give an indication on the performance of the Medi-Cult culture media. It appears that in countries were we have access to both national data from individual clinics, clinics using Medi-Cult media generally performs well.
The IVF-units in the Nordic countries use similar clinical and laboratory protocols and their patient populations are comparable.
The largest IVF clinics in Norway have been using only Medi-Cult media since the end of the 1980's. The results from cycles were cryopreserved embryos have been replaced can be obtained from The IVFunit, Dept of Obstetrics & Gynecology, University of Trondheim, Norway and The National Hospital, Oslo, Norway.
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K4911772
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Table 1a. The outcome after replacement of frozen/thawed IVF-embryos at the IVF-Unit, Dept of O University of Trondheim, Norway in the period 1988-1998
| Number of embryo replacements | Clinical pregnancies | Pregnancy rate per embryo replacement |
|---|---|---|
| 966 | 164 | 17.0 |
Table 1b. The outcome after replacement of frozen/thawed The National Hospital, Oslo, Norway in the period 1994-1996
| Number of embryoreplacements | Clinical pregnancies | Pregnancy rate per embryoreplacement |
|---|---|---|
| 465 | 85 | 18.3 |
The national average for Norway is not meaningful since the two other clinics cryopreserving embryos The national average 101 Not way is not meaning in suregnancies 8.1% pregnancy rate)
In Sweden, the Carl von Linne Clinic uses only products from Medi-Cult for culture of gametes and In Sweden, the Carl von Limic ases only products from the area.
embryos. For the year 1997 their birth rate per frozen embryo replacement was 22% (National data not available yet).
The Human Fertilisation and Embryology Authority (HFEA) in the UK, collects clinical data from all I he Human Fertinsation and Den for infertility by assisted reproduction.
HFEA publishes these data in a booklet and on the web. The clinical data are presented both unadjusted and adjusted for the demographics of the clinics patient population.
In the Table below the clinical data from some UK-clinics that use only Medi-Cult products is shown.
Table 2. Live birth rates per embryo replacement obtained in IVF units in the UK in the period April 1* 1996 to March 31st. 1997.
| Name of clinic | Number of FER*-cycles | Live birth rate per embryoreplacement % |
|---|---|---|
| Chelsea and Westminster Hospital | 24 | 20.8 |
| CARE at Park Hospital | 95 | 20.0 |
| The Woking Nuffield Hospital | 38 | 15.8 |
| Leeds General Infirmary | 333 | 14.1 |
| Nurture | 104 | 7.8 |
| Holly House Fertility and IVF | 115 | 17.4 |
| Guy's and St Thomas Assisted Conception Unit | 651 | 27.1 |
| UK national average | 4646 | 12.1 |
*FER: Frozen embryo replacement
There have been no registered complaints on the product and no evidence in the last 1.5 year that the I here have been the cause of any serious adverse events in connection with its intended use.
Thus based on the Federal Register Notice (Final Rule, Vol. 63, No. 175, page 48429, September 10, I illus Dased on the Pederal Register Frontes (Reclassification of Medical Devices Useries Useries 1970), "Obsteric and Oyneedoge Do Aces, ed Reproduction Procedures" effective on October 13, 1998 101 the supportive clinical data we feel that the safety and effectiveness of the product for its intended use is shown in the present submission.
Prepared and Submitted by:
Date
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K441472
Page 3 of 3
B5. 510(k) Summary
510(k) Summary Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination
The media "Medi-Cult Embryo Freezing Medium" is for freezing of embryos for support of In-Vitro fertilisation has been used extensively over a number of years to the satisfaction of the users at the IVF- and ART- clinics and laboratories.
There have been no registered complaints on the product and no evidence in the last 1.5 year that the product has been the cause of any serious adverse events in connection with its intended use.
A number of trials have shown that The Medi-Cult Embryo Freezing Medium performs well. (see Clinical Testing section reference list). A number of publications in peer- reviewed books or journals have presented data using Medi-Cult media. Often more than one product from Medi-Cult has been used in the studies listed.
Thus based on the Federal Register Notice (Final Rule, Vol. 63, No. 175, page 48429, September 10, 1998), "Obstetric and Gynecologic Devices; Reclassification and Classification of Medical Devices Used for In-Vitro Fertilization and Related Assisted Reproduction Procedures" effective on October 13, 1998 and the supportive clinical data we feel that the safety and effectiveness of the product for its intended use is shown in the present submission.
Prepared and Submitted by:
Ronald G., Leonardi, Ph. D. April 13, 1999
Date
President R & R Registrations P.O. Box 262069 San Diego CA 92196 1-619-586-0751
Date
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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract image of an eagle.
Public Health Service
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
MAY - 9 2000
Medi-Cult A/S c/o Ronald G. Leonardi, Ph.D. R & R Registrations P.O. Box 262069 San Diego, CA 92196-2069
Re: K991472 Medi-Cult Embrvo Freezing Medium Dated: April 3, 2000 Received: April 4, 2000 Requlatory Class: Il 21 CFR §884.6180/Procode: 85 MQL
Dear Dr. Leonardi:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce pror to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmelic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class III (Premarket Aproval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under Radiation Control provisions, or other Federal laws or regulations.
This letter will allow you to begin marketing your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4591. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.qov/cdrh/dsmamain.html".
Sincerely yours,
Daniel G. Schultz, M.D. Captain, USPHS Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure(s)
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510(k) Number (if known): K991472
Device Name: Medi-Cult Embryo Freezing Medium
Indications for Use:
Medi-Cult Embryo Freezing Medium" is for freezing of early (2-8 cell stage) embryos.
(PLEASE DO NO WRITE BELOW THIS LINE -- CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use
Optional Format 1-2-96)
(Division Sign-Off)
Division of Reproductive, Abdominal, ENT,
and Radiological Devices
510(k) Number K991472
§ 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.