(315 days)
Freezing Pack is for freezing of 1-4 cell stage embryos.
Thawing Pack is for thawing of embryos.
The products:
.
:" ,
- "Medi-Cult Freezing Pack with EFM" Cat.No. 1026 -
- "Medi-Cult Thawing Pack with EFM and IVF" Cat.No 1063 -
- "Medi-Cult Thawing Pack with EFM" Cat.No 1098 -
Products formulation: All products are based on Embryo Freezing Medium (EFM)
The Freezing Packs contains 3 different solutions reflecting a 3-step procedure and 4 vials:
- 1 x Vial 1: Embryo Freezing Medium (EFM) .
- 1 x Vial 2: EFM and propanediol .
- 2 x Vial 3; EFM, propanediol and Sucrose. ●
For thawing the Thawing Packs are used. They are composed as follows:
- Vial 1: Embryo Freezing Medium (EFM), propanediol and sucrose. ◆
- Vial 2: EFM, propanediol and Sucrose. .
- . Vial 3: EFM and Sucrose.
- Vial 4: EFM (Cat.No. 1098) or Universal IVF Medium (Cat.No. 1063) .
Product testing control contents:
- Bioburden, production-test -
- -Integrity filter testing, production-test
- -Sterility, OC-test
- pH, QC-test -
- Osmolarity, OC-test -
- Endotoxin, QC-test ﮯ
The provided text is a 510(k) summary for Medi-Cult Freezing and Thawing Packs, an in vitro fertilization (IVF) product. It describes the product's formulation, indications for use, and quality control tests, and then presents clinical data from IVF clinics as evidence of its performance.
Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria, based on the provided text, formatted as requested:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific pregnancy rates or live birth rates that the device must achieve to be considered effective. Instead, it presents clinical data from various clinics using Medi-Cult products and compares these results implicitly against national averages or other clinics where available. The underlying acceptance criterion appears to be that the device performs at least comparably to established IVF practices or predicate devices.
| Acceptance Criterion (Implicit) | Reported Device Performance (Pregnancy/Live Birth Rates with Medi-Cult Products) |
|---|---|
| Comparable pregnancy rate per embryo replacement | Trondheim, Norway (1988-1998): 17.0% (n=966 embryo replacements) |
| Oslo, Norway (1994-1996): 18.3% (n not fully specified, but implies good performance vs. national average of 8.1% for other clinics) | |
| Comparable live birth rate per embryo replacement | Carl von Linne Clinic, Sweden (1997): 22% (per frozen embryo replacement) |
| UK Clinics (April 1996-March 1997): - Chelsea and Westminster Hospital: 20.8% - CARE at Park Hospital: 20.0% - The Woking Nuffield Hospital: 15.8% - Leeds General Infirmary: 14.1% - Nurture: 7.8% - Holly House Fertility and IVF: 17.4% - Guy's and St Thomas Assisted Conception Unit: 27.1% | |
| Overall performance comparable to UK national average | Several UK clinics using Medi-Cult products show performance above the UK national average of 12.1% (e.g., Chelsea, CARE, Guy's and St Thomas). Some are below. |
| No serious adverse events | No registered complaints and no evidence of serious adverse events in the last 1.5 years. |
2. Sample Size Used for the Test Set and Data Provenance
The "test set" in this context refers to the clinical data used to support the safety and effectiveness.
- Trondheim, Norway: 966 embryo replacements. Data provenance: Norway, retrospective (1988-1998).
- Oslo, Norway: Number of embryo replacements not explicitly stated in the table, but the rate of 18.3% is given. Data provenance: Norway, retrospective (1994-1996).
- Carl von Linne Clinic, Sweden: "birth rate per frozen embryo replacement was 22%" for the year 1997. Specific number of replacements not stated. Data provenance: Sweden, retrospective (1997).
- UK Clinics: Total of 1,360 "frozen embryo replacement" (FER) cycles across 7 clinics. Data provenance: UK, retrospective (April 1, 1996 to March 31, 1997).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- The document implies that the ground truth (clinical pregnancy and live birth outcomes) was established by the clinics themselves as part of their standard clinical practice and reporting.
- No specific number of experts or their qualifications for establishing the ground truth for the test set (as in, for a specific study design with independent adjudication) are mentioned. The data are "clinical data from clinics" and "national data," suggesting routine clinical outcomes reported by the medical staff (e.g., obstetricians, gynecologists, embryologists) at those IVF units.
4. Adjudication Method for the Test Set
- No specific adjudication method (e.g., 2+1, 3+1) is mentioned or implied. The data appear to be raw reported clinical outcomes directly from the IVF clinics or national registries. This is typical for retrospective analyses of real-world clinical performance.
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 MRMC or AI-assisted study was performed. These are cryopreservation media, not AI-driven diagnostic or assistive devices.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
- This is not applicable to a cryopreservation media product. The "device" is a physical product (liquid media), not an algorithm.
7. The Type of Ground Truth Used
- The ground truth used is clinical outcomes data, specifically:
- Clinical pregnancies (defined as positive pregnancy test confirmed by ultrasound)
- Live birth rates (birth of a live infant)
- These are based on actual patient results from IVF treatments using the Medi-Cult products.
8. The Sample Size for the Training Set
- This concept is not applicable as this is not an AI/machine learning device. The product formulation was developed based on published scientific data and established IVF practices ("formulated according to data published in peer-reviewed international journals by internationally recognised scientists in the field"). There isn't a "training set" in the computational sense.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. The "ground truth" for the development of the media would be the scientific understanding of cryopreservation principles for embryos, established through decades of research and clinical practice in reproductive medicine, rather than a specific "training set" with ground truth established for an algorithm.
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510(k) Summary Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination (K991335)
The products:
.
:" ,
- "Medi-Cult Freezing Pack with EFM" Cat.No. 1026 -
- "Medi-Cult Thawing Pack with EFM and IVF" Cat.No 1063 -
- "Medi-Cult Thawing Pack with EFM" Cat.No 1098 -
Indication for use:
Medi-Cult Freezing Pack" is for freezing of 1-4 cell stage embryos, & Medi-Cult Thawing Pack" is for thawing of embryos.
Products formulation: All products are based on Embryo Freezing Medium (EFM)
The Freezing Packs contains 3 different solutions reflecting a 3-step procedure and 4 vials:
- 1 x Vial 1: Embryo Freezing Medium (EFM) .
- 1 x Vial 2: EFM and propanediol .
- 2 x Vial 3; EFM, propanediol and Sucrose. ●
For thawing the Thawing Packs are used. They are composed as follows:
- Vial 1: Embryo Freezing Medium (EFM), propanediol and sucrose. ◆
- Vial 2: EFM, propanediol and Sucrose. .
- . Vial 3: EFM and Sucrose.
- Vial 4: EFM (Cat.No. 1098) or Universal IVF Medium (Cat.No. 1063) .
Product testing control contents:
- Bioburden, production-test -
- -Integrity filter testing, production-test
- -Sterility, OC-test
- pH, QC-test -
- Osmolarity, OC-test -
- Endotoxin, QC-test ﮯ
The culture media from Medi-Cult have been used by many European IVF-units since the end of the 1980's. (Produced and distributed by GEA-Biotech 1987 to 1989 and by Medi-Cult als from 1989). The Medi-Cult media were at that time introduced as a replacement for in-house prepared culture media. The Medi-Cult products for cryopreservation is in general formulated according to data published in peer reviewed international journals by internationally recognised scientists in the field.
The clinical date shown below comes from clinics using one or several of these products for cryopreservation of zygotes and embryos: The Medi-Cult Embryo freezing medium; The Medi-Cult Embryo freezing pack; The Medi-Cult Embryo thawing pack with EFM and IVF-medium.
We have collected clinical data from clinics that use only products from Medi-Cult. The data from cycles with replacement of cryopreserved embryos are in general not reported as the data from replacement of fresh IVF/ICSI embryos. Consequently, national data can be difficult to obtain.
A comparison of the clinical performance of clinics using only Medi-Cult media with other IVF-clinics using similar clinical and laboratory routines can give an indicate on the performance of the Medi-Cult culture media. 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.
Table1. The outcome after replacement of frozen/thawed IVF-embryos at the IVF-Unit, Dept of Ob. & Gyn. University of Trondheim, Norway in the period 1988-1998.
| Number of embryo replacements | Clinical pregnancies | Pregnancy rate per embryo replacement |
|---|---|---|
| 966 | 164 | 17.0 |
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| rantTable 2. The outcome after replacement of frozen/thawed The National Hospital, Oslo, Norway 1994-1996. ' | ||||
|---|---|---|---|---|
| Number of embryo replacements Clinical pregnancies | Pregnancy rate per embryo | |||
| ren acement |
18.3
કર્ The national average for Norway is not meaningful since the two other clinics cryopreserving embryos only performed a few cycles (1994 -1996: 37 cycles/ 3 pregnancies 8.1% pregnancy rate)
In Sweden, the Carl von Linne Clinic uses only products from Medi-Cult for culture of gametes and embryos. For the year 1997 their birth rate per frozen embryo replacement was 22% (National data not available),
The Human Fertilisation and Embryology Authority (HFEA) of the UK, collects clinical data from all centres licensed to offer treatment for infertility by assisted reproduction. HFEA publishes these and on the web. The clinical data are presented both unadjusted 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. These clinics have all given their consent to be presented as clinics using only Medi-Cult products.
Table 3. Live birth rates per embryo replacement in IVF units in the UK April 1, 1996 to March 31, 1997.
| Name of clinic | Number of FER*-cycles | Live birth rate per embryo replacement % |
|---|---|---|
| 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 embrvo replacement
465
The Medi-Cult Blastocyst Freezing and Thawing pack has recently been introduced for cryopreservation and thawing of human blastocyst. This product is based on the work of Yves Menezo and co workers who has developed a protocol for freezing and thawing of human blastocysts. (Y.Menezo et al., In Proceedings of ASRM, Boston, 1996 & Y.Menezo & A.Veiga. In Proc. of 10th World Congress of IVF & Assisted Reproduction, Vancouver (Canada), May 1997). Since introduction of a commercially available product identical to the formulation of Menezo and co-workers, many clinics have started to use The Medi-Cult Blastocyst Freezing and Thawing pack. Clinical data available indicates that our product has the same performance as indicated by Menezo.
There have been no registered complaints on the product and thus no evidence in the last 1.5 years that the product has 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, 1998), "Obstetric and Gynecologic Devices; Reclassification 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.
Date
Prepared and Submitted by:
Keen Wüher-Lousada for February 18, 2000
Ronald G. Leonardi, Ph. D. President R & R Registrations P.O. Box 262069 San Diego CA 92196 1-858-586-0751
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Public Health Service
DEPARTMENT
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
FEB 2 8 2000
Medi-Cult A/S c/o Ronald G. Leonardi, Ph.D. President R & R Registrations P.O. Box 262069 San Diego, CA 92196
Re: K991335
Medi-Cult Freezing and Thawing Packs Dated: December 14, 1999 Received: December 15, 1999 Regulatory 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 prior 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 Cosmetic 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 practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), 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 the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
This letter will allow you to begin marketing your device as described in 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.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Daniel G. Schultz, M.D.
Daniel G. Schultz, M.D Captain, USPHS Acting 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) K991335
Device Name: Medi-Cult Freezing Pack and Thawing Pack Indications for Use:
Freezing Pack is for freezing of 1-4 cell stage embryos.
Thawing Pack is for thawing of 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 K991335
§ 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.