MEDI-CULT SPERM FREEZE MEDIUM

K991333 · Medicult A/S · MQL · Feb 28, 2000 · Obstetrics/Gynecology

Device Facts

• Record ID: K991333
• Device Name: MEDI-CULT SPERM FREEZE MEDIUM
• Applicant: Medicult A/S
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Feb 28, 2000
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

Medi-Cult Sperm Freeze Medium is intended for the cryopreservation of human spermatozoa and tissue from testicular biopsies.

Device Story

Medi-Cult Sperm Freezing Medium (SFM) is a cryopreservation solution for human spermatozoa and testicular biopsy tissue. The formulation consists of a modified Tyrodes solution with HEPES buffer, 15% v/v glycerol as the cryoprotective agent, and additives including Assisted Reproduction Technique Supplement (ARTS) and human serum albumin (HSA). The device is used in clinical laboratory settings to prepare sperm for long-term storage. By protecting cellular integrity during freezing and thawing, the medium maintains sperm motility, viability, and functional capacity, specifically the ability to bind to the zona pellucida. Healthcare providers use the medium to process samples, which are then frozen; the resulting preserved samples are used in assisted reproductive procedures. The product is intended to support successful fertilization outcomes by minimizing the detrimental effects of cryopreservation on sperm receptors and cellular structures.

Clinical Evidence

Clinical evidence includes comparative studies against TEST-Yolk buffer (TYB). A study at the University of Rochester Medical Center (n=not specified) compared motility, viability, normal cell percentage, and straight-line velocity (VSL), finding no significant differences between SFM and TYB. A hemi-zona assay (HZA) conducted at The Jones Institute for Reproductive Medicine compared sperm binding ability; SFM showed significantly higher binding (149.0 ± 10.4) compared to TYB (103.9 ± 6.0) with p < 0.0001. Other parameters including velocity, beat amplitude, frequency, linearity, and hyperactivation showed no significant differences between the two media.

Technological Characteristics

Formulation: Modified Tyrodes solution, HEPES buffer, 15% v/v glycerol, Assisted Reproduction Technique Supplement (ARTS), and human serum albumin (HSA). The medium is a liquid chemical solution. Quality control testing includes bioburden, integrity filter testing, sterility, pH, endotoxin, and sperm survival. No electronic, mechanical, or software components.

Indications for Use

Indicated for the cryopreservation of human spermatozoa and tissue from testicular biopsies.

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.

Reference Devices

• TEST-Yolk buffer (TYB, Irvine Scientific)

Submission Summary (Full Text)

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#### 510(k) Summary Summary of Safety and Effectiveness Information FEB 2 8 2000 Supporting a Substantially Equivalent Determination (K991333)

## The product

"Medi-Cult Sperm Freeze Medium" Cat.No. 1067 -

#### Indications for use:

"Medi-Cult Sperm Freeze Medium" is intended for the cryopreservation of human spermatozoa and tissue from testicular biopsies.

#### The product formulation:

Modified Tyrodes with HEPES buffer containing sucrose, glucose and sodium lactate Assisted Reproduction Technique Supplement, (ARTS) Glycerol Human Serum Albumin (HSA) Penicillin Streptomycin

#### The product testing control contents:

- Bioburden, production-test
- -Integrity filter testing, production-test
- Sterility, QC-test .
- pH, QC-test
- Endotoxin, QC-test ・
- -Sperm Survival, QC-test

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 a/s 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 iournals by internationally recognised scientists in the field.

Medi-Cult has recently introduced a medium for the crypreservation of human spermatozooa. Medi-Cult Sperm Freezing Medium (SFM) is composed from a modified Tyrodes Solution that has been Hepes buffered. The cryoprotective is Glycerol (15% v/v) and its crypprotective properties have been enhanced by the addition of Assisted Reproduction Technique Supplement (ARTS) and human serum albumin.

The product contains small amounts of potentially hazardous Human Serum Albumin, which has been obtained from a U.S licensed source (U.S license No.140). It origins from larger pools of screened healthy donors, tested negative for HBbsAg, Anti-HCV, anti HIV-1/2. Levels of ALT (GPT) in the plasma are determined and donations are rejected if the values found are above the upper limit of the specifications. Donors of the source material have been screened for CJD.

At the Rochester Regional Cryobank and Andrology Laboratory, University of Rochester Medical center, Rochester, NY, the Medi-Cult Sperm Freezing medium have been compared with TEST-Yolk buffer (TYB, Irvine Scientific, Irvine CA). The following results were obtained:

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| | Motility % | Viability % | Normal cells % | VSL* |
|-------------|------------|-------------|----------------|------------|
| Fresh semen | 61.1(3.6) | | 50.0 (6.1) | 43.1 (3.1) |
| SFM** | 20.6(2.4) | 40.7(4.2) | 53.8(5.1) | 31.5(1.5) |
| TYB *** | 19.1 (1.0) | 49.6(1.7) | 49.3(5.5) | 29.7(1.6) |

### *VSL: straight line velocity

**SFM: Sperm Freezing Medium from Medi-Cult

***TYB: TEST-Yolk buffer from Irvine Scientific

No differences between sperm frozen with SFM or with TYB were found in this study.

Binding of the spermatozoa to the zona pellucida (ZP) is a necessary step in fertilisation both in vivo and in vitro (IVF). Freezing/thawing might have a detrimental effect on the receptors on the surface of sperm cells and thus impair binding to the zona pellucida. Dr Mary Mahonev at The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, USA, have evaluated the ability of frozen/thawed spermatozoa to bind to isolated zona pellucidae using the "hemi-zona assay". Sperm frozen and thawed in Medi-Cult Sperm Freezing medium and in TEST-Yolk buffer form Irvine Scientific was compared.

## Table 1. Hemi-zona assay (HZA) after freezing/thawing in Sperm Freezing Medium from Medi-Cult (SFM) or TEST-Yolk buffer from Irvine Scientific (Test-Yolk)

| HZA binding in TEST-Yolk | HZA Binding in SFM | HZA-SFM/HZA-TEST-yolk % |
|--------------------------|--------------------|-------------------------|
| Mean ± SE | Mean ± SE | Mean ± SE |
| 103.9 ± 6.0 | 149.0 ± 10.4* | 152.3 ± 10.2 |

#### *Significantly higher than in Test-Yolk buffer p< 0.0001

Dr. Mahoney also compared other parameters such as motility, velocity (+VSL and VCL) beat amplitude (ALH) and frequency (BCF), linearity (LIN) and hyperactivation (HA) and found no differences between sperm frozen in SFM or in TEST-Yolk buffer.

There have been no registered complaints on the product and there is 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.

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 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:

Rice Wickey-Lermaid for feruary 18, 2018
Ronald G. Leonardi, Ph. D.
Date

President R & R Registrations P.O. Box 262069 San Diego CA 92196 858-586-0751

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Public Health Service

Rockville MD 20850

Food and Drug Administration 9200 Corporate Boulevard

Image /page/2/Picture/2 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the circle is an abstract image of an eagle.

FEB 28 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: K991333

Medi-Cult Sperm Freeze Medium Dated: December 14, 1999 Received: December 15, 1999 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 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 (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 Requiations, 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 vour 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 diacnostic devices), please contact the Office of Compliance at [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 Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

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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#### K991333 510(k) Number (if known):

# Device Name: MEDI-CULT SPERM FREEZING MEDIUM (SFM)

Indications for Use:

For the cryopreservation of human spermatozoa and tissue from testicular biopsies.

(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 K991333