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.

AI/ML Overview

Here's an analysis of the provided text regarding the SynVitro® Hyadase device, focusing on acceptance criteria and supporting studies:

This document describes a 510(k) submission for a medical device, SynVitro® Hyadase, which is a hyaluronidase product used for denuding oocytes (removing surrounding cells) prior to Intracytoplasmic Sperm Injection (ICSI). The submission focuses on demonstrating substantial equivalence to a predicate device.

Key takeaway: The provided text describes a comparative effectiveness study to demonstrate substantial equivalence to a predicate device, rather than a study defining and meeting de novo acceptance criteria for a novel device. The acceptance criteria are implicitly based on the predicate device's performance regarding morphological quality of embryos, fertilization rate, and cleavage rate.

Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implicit from Predicate Equivalence)	Reported SynVitro® Hyadase Performance
Morphological quality of embryos (equivalent to predicate)	No significant difference
Fertilization rate (equivalent to predicate)	No significant difference
Cleavage rate (equivalent to predicate)	No significant difference

Study Details

1. Sample size used for the test set and the data provenance:

Test Set Sample Size: Not explicitly stated. The text mentions "Two comparable groups of oocytes were inseminated." and "a randomised clinical study has been performed comparing SynVitro® Hyadase... to Medi-Cult's Hyaluronidase product." Without specific numbers, the exact sample size cannot be determined from this document.
Data Provenance: Not explicitly stated (e.g., country of origin). Both studies are described as "clinical studies." It is implied to be prospective since it's a comparative study.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Number of Experts: Not mentioned.
Qualifications of Experts: Not mentioned. Given the nature of assessing embryo morphology, fertilization, and cleavage rates, it would typically involve embryologists or fertility specialists, but this is not specified.

3. Adjudication method for the test set:

Adjudication Method: Not mentioned.

4. 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:

MRMC Study: No, this does not appear to be an MRMC study. This device is a biochemical product (hyaluronidase), not an AI algorithm or an imaging device requiring human reader interpretation in the context of an MRMC study.
Effect Size: Not applicable.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Standalone Performance: Not applicable. This is not an algorithm.

6. The type of ground truth used:

The "ground truth" for the comparative studies was based on clinical outcomes relevant to assisted reproductive technology:
- Morphological quality of the embryos
- Fertilization rate
- Cleavage rate

7. The sample size for the training set:

Training Set Sample Size: Not applicable. This submission describes a clinical study to compare a new product to a predicate, not a machine learning model that requires a training set.

8. How the ground truth for the training set was established:

Ground Truth for Training Set: Not applicable.

Summary of Device Performance and Equivalence:

The provided clinical documentation indicates that two comparative studies were conducted:

Comparison of Hyaluronidase Sources: This study compared hyaluronidase from two different sources (one being SynVitro® Hyadase's non-bovine source) and found no significant difference in morphological quality of embryos, fertilization rate, and cleavage rate.
Comparison to Predicate Device (Medi-Cult's Hyaluronidase): This randomized clinical study compared SynVitro® Hyadase (without HSA) to the predicate Medi-Cult Hyaluronidase (with HSA). The results indicated that both products were "equally effective" regarding morphological quality of the embryos, fertilization rate, and cleavage rate.

Based on these studies, the manufacturer concluded that SynVitro® Hyadase is substantially equivalent to the predicate device K991334 (Medi-Cult Hyaluronidase) and effective for its intended use. The FDA concurred with this determination.

Summary

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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.

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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	(301) 594-4591
876.2xxx, 3xxx, 4xxx, 5xxx	(301) 594-4616
884.2xxx, 3xxx, 4xxx, 5xxx, 6xxx	(301) 594-4616
892.2xxx, 3xxx, 4xxx, 5xxx	(301) 594-4654
Other	(301) 594-4692

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 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 (800) 638-2041 or (301) 443-6597 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)

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

Regulation Number and Section

§ 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.