MEDI-CULT UNIVERSAL IVF-MEDIUM

K991279 · Medicult A/S · MQL · Jul 20, 2000 · Obstetrics/Gynecology

Device Facts

• Record ID: K991279
• Device Name: MEDI-CULT UNIVERSAL IVF-MEDIUM
• Applicant: Medicult A/S
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Jul 20, 2000
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

Medi-Cult Universal IVF Medium is used for the fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage (day 2 after insemination). Medi-Cult Universal IVF Medium can also be used as vehicle during embryo transfer.

Device Story

Medi-Cult Universal IVF Medium is a liquid culture medium used in assisted reproduction technology (ART) clinics. It supports fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage; it also serves as a vehicle for embryo transfer. The medium is formulated with Earl's Balanced Salt Solution (EBSS), sodium pyruvate, sodium bicarbonate, and human serum albumin (HSA). Specific variants exclude penicillin/streptomycin or phenol red. The device is used by embryologists and clinicians in laboratory settings to maintain oocyte/embryo viability during in vitro procedures. Clinical performance is monitored via live birth rates per started cycle or embryo replacement. The medium replaces in-house prepared culture media, providing a standardized environment for gamete and embryo development.

Clinical Evidence

Clinical evidence includes retrospective data from multiple European IVF clinics (Norway, Sweden, UK) using Medi-Cult media. Data from 1992-1996 in Norway showed live birth rates per started cycle ranging from 11.4% to 25.35%. 1997 data from a Swedish clinic reported a 34% birth rate per embryo replacement. UK data (1996-1997) across multiple centers showed live birth rates per embryo replacement ranging from 22.3% to 34.5%, generally exceeding the UK national average of 21.8%. No serious adverse events reported in the 1.5 years prior to submission.

Technological Characteristics

Formulated with Earl's Balanced Salt Solution (EBSS), sodium pyruvate, sodium bicarbonate, and human serum albumin (HSA). Variants available without penicillin/streptomycin or phenol red. Quality control testing includes bioburden, filter integrity, sterility, pH, osmolarity, endotoxin levels, and mouse embryo (two-cell) assay (>80% hatched).

Indications for Use

Indicated for fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage (day 2 post-insemination) and as a vehicle during embryo transfer in patients undergoing assisted reproduction procedures.

Regulatory Classification

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.).

Special Controls

*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.

Submission Summary (Full Text)

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### 510(k) Summary Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination (K991279)

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#### The products:

- "Medi-Cult Universal IVF Medium" Cat.No. 1031 -
- "Medi-Cult Universal IVF Medium w/o Phenol" Cat.No. 1030 -
- "Medi-Cult Universal IVF Medium w/o Pen/Strep" Cat.No. 1095 -

#### Indications for use:

"Medi-Cult Universal IVF Medium" is for fertilisation of human oocytes and culture of fertilised oocytes up to the 4-6-cell stage (day 2 after insemination). "Medi-Cult Universal IVF Medium" can also be used as vehicle during embryo transfer.

#### Product formulation:

Earl's Balanced Salt Solution (EBSS) Sodium Pyruvate Assisted Reproduction Technology Supplement (ARTS) Sodium Bicarbonate Human Serum Albumin (HSA) Penicillin (Except product 1095) Streptomycin (Except product 1095) Phenol Red (Except product 1030)

#### Product testing control contents:

- Bioburden, production-test -
- Integrity filter testing, production-test -
- ー Sterility. QC-test
- pH, QC-test
- Osmolarity, QC-test -
- -Endotoxin, QC-test
- Mouse Embryo, (two cells assay; > 80% hatched) QC-test -

The culture media from Medi-Cult have been used by many European IVF-units since the end of 1980. (Produced and distributed by GEA-Biotech 1987 to 1989 and by Medi-Cult a/s from 1989). The Medi-Cult media were at that time introduced as a replacement for in-house prepared culture media.

A number of prospective randomized trials have shown that The Medi-Cult-IVF-medium performs equally well or better than altemative culture media. A number of publications in peerreviewed books or journals have presented data using Medi-Cult media.

The clinical result of a given IVF-clinic will depend on the patient population treated, the clinical procedures, 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. In countries where we have access to both national data from individual clinics, clinics using Medi-Cult media generally perform well.

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K 991279
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The IVF-units in the Nordic countries use similar clinical and laboratory protocols and their patient populations are comparable. The clinical data from most Nordic countries are available. In some countries the performance of individual IVF-clinics are available.

The largest IVF clinics in Norway have been using only Medi-Cult media since the end of the 1980's. The data collected in the years from 1992 to 1996 are shown below as live birth rates per started cycle.

| Clinic | 1992 | 1993 | 1994 | 1995 | 1996 |
|-------------------------------------|------|------|------|-------|------|
| Dept of Ob & Gyn, Univ of Trondheim | 22.2 | 22.2 | 19.8 | 25.35 | 18.4 |
| The National Hospital, Oslo | 13.3 | 19.0 | 15.8 | 11.42 | 17.4 |
| National average | 14.6 | 17.5 | 17.9 | 16.84 | 16.3 |

| Table 1. Live birth rates per started cycle obtained in IVF units in Norway | | | |
|-----------------------------------------------------------------------------|--|--|--|
|-----------------------------------------------------------------------------|--|--|--|

In Sweden, the Carl von Linne Clinic uses only products from Medi-Cult for culture of gametes and embryos. For the vear 1997 their birth rate per embryo replacement was 34% their clinical results were the best in Sweden and well above the national average of 25.8%.

The Human Fertilization and Embryology Authority (HFEA) in the UK collects clinical data from all centers licensed to offer treatment for infectility 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. These clinics have all given their consent to be presented as clinics using only Medi-Cult products.

Table 2. Live birth rates per embryo replacement obtained in IVF units in the period April 186 1996 to March 31, 1997.

| Name of clinic | Number of | Live birth rate per |
|----------------------------------------------|-------------|----------------------|
| | IVF- cycles | embryo replacement % |
| Northamptonshire Fertility service | 503 | 26.0 |
| The Bridge Centre | 852 | 27.2 |
| Chelsea and Westminster Hospital | 388 | 22.3 |
| CARE at Park Hospital | 650 | 34.5 |
| BMI Ross Hall Hospital | 68 | 27.5 |
| The Woking Nuffield Hospital | 163 | 32.6 |
| Leeds General Infirmary | 1434 | 24.0 |
| Nurture | 1245 | 28.8 |
| Holly House Fertility and IVF | 333 | 30.5 |
| Guy's and St Thomas Assisted Conception Unit | 651 | 27.1 |
| UK national average | 33520 | 21.8 |

There have been some registered complaints on the product but there is 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.

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K991279
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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:

Rune Wilhe-Leonardi 4/21/00
Ronald G. Leonardi, Ph. D. Date

Ronald G. Leonardi, Ph. D. President R & R Registrations P.O. Box 262069 San Diego CA 92196 858-586-0751

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Image /page/3/Picture/1 description: The image shows a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the edge. In the center of the seal is a stylized image of an eagle with its wings spread. The eagle is composed of three curved lines, and there are three wavy lines below the eagle, possibly representing water.

Public Health Service

JUL 2 0 2000

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Medi-Cult, A/S c/o Ronald G. Leonardi, Ph.D. R & R Registrations P.O. Box 262069 San Diego, California 92196-2069 Re: K991279 Medi-Cult Universal IVF-Medium-Assisted Reproduction Technology Supplement (ARTS) Dated: April 20, 2000 Received: April 21, 2000 Regulatory Class: II 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 we have reviewed your Occared or requireditions for use stated in the enclosure) to legally marketed predicate devices device is substantially equivately (10 the moducal of the Medical Device Amendments, or to devices that maneted in interstate conmisions of the Federal Food, Orug, and Cosmetic Act (Act (Act (Act (Act, You may, therefore, nave occh receasured in acorrance that all players of the Act. The general controls provisions of the Act Include mants the october to the goned condevies, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class III (Premarket Approval), it may be subject to il your device (see above) in oknier also title base the pyrum in the Code of Federal Requilations, This 21, Such additions Confiness Existing major regulations and the Current Good Manufacting Practice r ans oo oo oos. A Substantant Squalition (QS) for Medical Devices: General regulation (21 CFR Part 820) and requirements, as sections, 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 the Edefarmediate. Thease note the responses to Joines under the Electionic 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 r no to the nequivalence 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.

11 for in esire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for incritor ir you desire specific article for your do hassing of [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the million and be obtained to pivision of Small Manufacturers Assistance at its toll-free number [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsmaldsmamain.html".

Sincerely yours,

Daniel C. Schultz, M.D.

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): K991279

Device Name: Medi-Cult Universal IVF Medium

Indications for Use:

Medi-Cult Universal IVF Medium is used for the fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage {day 2 after insemination).

Medi-Cult Universal IVF Medium can also be used as vehicle during embryo transfer.

# (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 _________________________________________________________________________________________________________________________________________________________

David A. Elgerson

(Optional Format 1-2-96)

(Division Sign-Off) Division of Reproductive, Abdominal, ENT, and Radiological Devices 510(k) Number