SYNVITRO HYADASE

K031228 · Medicult A/S · MQL · Jun 24, 2003 · Obstetrics/Gynecology

Device Facts

• Record ID: K031228
• Device Name: SYNVITRO HYADASE
• Applicant: Medicult A/S
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Jun 24, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

SynVitro® Hyadase is for the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI.

Device Story

SynVitro® Hyadase is a ready-to-use hyaluronidase solution derived from a non-bovine source; used in clinical laboratory settings by embryologists to denude oocytes prior to ICSI. The solution facilitates the removal of the cumulus complex and corona radiata, allowing access to the oocyte for injection. It contains no human serum albumin (HSA) or antibiotics. The product is supplied as a liquid reagent; it does not have direct patient contact. Clinical benefit includes effective preparation of oocytes for fertilization procedures without significant differences in embryo quality, fertilization rates, or cleavage rates compared to HSA-containing alternatives.

Clinical Evidence

Clinical evidence includes two studies. First, a study comparing hyaluronidase from two different sources showed no significant difference in embryo morphological quality, fertilization rate, or cleavage rate. Second, a randomized clinical study compared SynVitro® Hyadase (no HSA) to the predicate Medi-Cult Hyaluronidase (contains HSA). Results confirmed the subject device is equally effective regarding embryo quality, fertilization rate, and cleavage rate. No serious adverse events or complaints were reported.

Technological Characteristics

Ready-to-use hyaluronidase solution (80 IU/ml) from non-bovine source. Ingredients: E ART supplement, glucose, sodium pyruvate, calcium chloride, magnesium sulphate, sodium chloride, sodium bicarbonate, HEPES. Does not contain HSA or antibiotics. Quality controls include sterility, pH, osmolality, and Mouse Embryo Assay (Blastocyst rate > 70%).

Indications for Use

Indicated for the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for intracytoplasmic sperm injection (ICSI).

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.

Predicate Devices

• Medi-Cult Hyaluronidase (K991334)

Submission Summary (Full Text)

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K031228

# JUN 2 4 2003

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

#### Intended use

SynVitro® Hyadase is for the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI.

#### Composition

- Hyaluronidase 80 IU/ ml (non-bovine source) 내
- E ART supplement
- 트 Glucose
- Sodium pyruvate I
- 트 Calcium chloride
- 트 Magnesium sulphate
- 트 Sodium chloride
- 피 Sodium bicarbonate
- 비 HEPES

### Biocompatibility testing

When following the procedure described in our package insert Syn Vitro@Hyadase will not have patient contact, thus biocompatibility testing has not been performed.

## Product testing controls

Sterility tested pH tested Osmolality tested Mouse Embryo Assay, (one cell assay, Blastocyst rate > 70 %) For each batch a Certificate of Analysis with the results of the above tests is available.

### Clinical Documentation:

Prior to the ICSI procedure, the cells of the cumulus and corona radiata must be removed in order to facilitate access to the oocyte and minimize contamination of the injection needle.

SynVitro® Hyadase is a ready-to-use hyaluronidase product designed for denudation of the oocyte and is based on raw material from a non-bovine source. SynVitro®Hyadase does not contain human serum albumin (HSA) or antibiotics.

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Hyaluronidase originating from two different sources were compared in a clinical study. Two comparable groups of oocytes were inseminated after the cumulus had been removed using one of the two sources of hyaluronidase. The result of the study showed that there was no significant difference between the two groups regarding the morphological quality of the embryos, the fertilisation rate and the clevage rate.

Furthermore a randomised clinical study has been performed comparing SynVitro® Hyadase, which does not contain human serum albumin (HSA) to Medi-Cult's Hyaluronidase product that contains HSA. The results of this study is that SynVitro® Hyadase and Medi-Cult Hyaluronidase are equally effective regarding the morphological quality of the embryos, the fertilisation rate and the cleavage rate.

Based on these studies it is concluded that SynVitro® Hyadase is substantial equivalent to Medi-Cult Hyaluronidase ( K 991334) and is effective for denuding oocytes prior to ICSI.

During our studies there has been no registered complaints and no evidence that the product has been the cause of any serious adverse events in connection with its intended use.

Thus based on the clinical data presented and our experience with the SynVitro®Hyadase product we feel that the safety and effectiveness of the product for its intended use is shown in the present submission and the product is substantially equivalent to the predicated device Medi-Cult Hyaluronidase ( K 991334).

Prepared and Submitted by:

Ronald G. Leonardi, Ph.D.

Ronald G. Leonardi. Ph.D. President R & R REGISTRATIONS P.O. Box 262069 San Diego, Ca 92131 619-586-0751

April 17, 2003
Date

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle or bird-like figure with three curved lines representing its wings or body.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

JUN 2 4 2003

Medi-Cult a/s % Ronald G. Leonardi, Ph.D. President R & R Registrations P.O. Box 262069 SAN DIEGO CA 92196-2069 Re: K031228 Trade/Device Name: SynVitro® Hyadase Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: II Product Code: 85 MQL Dated: April 18, 2003 Received: April 24, 2003

Dear Dr. Leonardi:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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. Iisting 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 (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (sections 531-542 of the Act); 21 CFR 1000-1050.

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This letter will allow you to begin marketing your device as described in your Section 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), please contact the Office of Compliance at one of the following numbers, based on the regulation number at the top of the letter:

| 8xx. 1xxx | [phone] |
|----------------------------------|----------------|
| 876.2xxx, 3xxx, 4xxx, 5xxx | [phone] |
| 884.2xxx, 3xxx, 4xxx, 5xxx, 6xxx | [phone] |
| 892.2xxx, 3xxx, 4xxx, 5xxx | [phone] |
| Other | [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 Part 807.97) you may obtain. Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers. International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Nancy C. Brogdon

Nancy C. Brogdon Director, Division of Reproductive. Abdominal and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

Page 2

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#### k031228 510(k) Number (if known)

SynVitro®Hyadase Device Name:

# INDICATIONS FOR USE:

For the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI.

(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)

Jancy C. Hayden

(Division Sign-Off) / Division of Reproductive, Abdominal, and Radiological Devi 510(k) Number