Hyaluronidase Solution is intended for use in assisted reproductive technology procedures involving the manipulation of gametes or embryos. Specifically, Hyaluronidase Solution is intended for use in removing cumulus cells surrounding oocytes (denudation) in preparation for ICSI or other ART procedures.

Device Description

Hyaluronidase Solution is a enzymatic solution containing 80 U/mL of bovine derived hyaluronidase in a HEPES buffered HTF Medium supplemented with 5.0 mg/mL (or 0.5%) therapeutic grade human serum albumin (HSA) and 10µg/mL gentamicin sulfate.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the Hyaluronidase Solution:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied)	Reported Device Performance
Support embryonic growth (absence of toxicity)	Assured by Mouse Embryo Assay (prior to release)
Removal of cumulus cells within 30-60 seconds (denudation)	Enzymatic digestion and removal occur within 30-60 seconds
No toxic components present	Assured by Mouse Embryo Assay (prior to release)
Suitability for intended use (denudation for ART procedures)	Validated by historical clinical use and performance testing
Meets criteria outlined in Notice of Final Rule, 63 FR 48428, Docket 97N-0335	Conclusion states the device meets these criteria

Note: The document does not explicitly list numerical acceptance criteria in a table format. The criteria are inferred from the "Performance Data" and "Conclusion" sections. For example, "support embryonic growth" is an implied criterion, and the "Mouse Embryo Assay" is the test mechanism.

2. Sample Size Used for the Test Set and Data Provenance

The document does not specify a distinct "test set" in the conventional sense (e.g., a specific number of oocytes or embryos used in a formal clinical trial for this submission).

Sample Size: Not explicitly stated as a separate "test set" for the current submission. The "Mouse Embryo Assay" is mentioned, but its sample size for the purpose of this submission is not detailed. The "equivalent of Hyaluronidase Solution" has been used in "a variety of clinical settings for a number of years," implying historical clinical data but without specific sample sizes or structured test sets for this particular submission.
Data Provenance: The document refers to the "equivalent of Hyaluronidase Solution" being used in "clinical settings," suggesting real-world use. This points towards retrospective observational data or historical experience. No specific country of origin is mentioned for this historical use, but the submitting company is US-based.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

Not applicable for this submission. The "ground truth" for regulatory approval here is primarily based on pre-clinical lab assays (Mouse Embryo Assay) and historical clinical performance of similar products, rather than a human expert consensus on diagnostic results.

4. Adjudication Method for the Test Set

Not applicable. There's no human expert adjudication process described for the performance data presented.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. An MRMC comparative effectiveness study was not performed. This type of study is more common for diagnostic imaging AI devices where human reader performance is a key metric.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, in essence. The "Performance Data" section describes a standalone assay (Mouse Embryo Assay) that the product undergoes prior to release to market. This assay directly assesses the product's biological impact (support for embryonic growth, absence of toxicity) independent of human intervention in its evaluation for the purpose of this submission. The enzymatic action for denudation is also an inherent, standalone function of the solution.

7. The Type of Ground Truth Used

The ground truth used is a combination of:

Biological Assay Results: Specifically, the Mouse Embryo Assay, which indicates the product's ability to support embryonic growth and its non-toxicity.
Historical Clinical Use/Outcomes Data: The document states the "equivalent of Hyaluronidase Solution has been used in a variety of clinical settings for the same intended use for a number of years," implying that successful outcomes from these real-world uses serve as a form of ground truth for its efficacy and safety.
Enzymatic Activity: The inherent function of the enzyme to digest cumulus cells is a direct measure of its intended effect.

8. The Sample Size for the Training Set

Not applicable. This device is a biological solution, not an AI/ML algorithm requiring a training set in the computational sense. The "training" here would be analogous to product development and formulation.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as it's not an AI/ML algorithm with a training set. The "ground truth" for the development and formulation of such biological media is established through biomedical research, standard laboratory protocols, and ensuring the final product meets functional and safety standards (e.g., appropriate enzyme concentration, sterility, pH, osmolality, and efficacy in cell removal and embryo viability). These are typically based on well-understood biological principles and established protocols in reproductive biology.

Summary

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510(k) SUMMARY AS REQUIRED BY SECTION 807.92(c)

Submitted by:	Irvine Scientific Sales Co., Inc.2511 Daimler StreetSanta Ana, CA 92705-5588Telephone: (800) 437-5706Facsimile: (949) 261-6522Contact: Wendell Lee, Pharm. D.Date Submitted: October 9, 2000	NOV 4 2002
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Device Identification:

Trade Name:	Hyaluronidase Solution
Common Name:	Hyaluronidase Solution
Classification Name:	Reproductive Media (21 CFR, 884.6180)

Predicate Device:

Notice of Final Rule, 63 FR 48428, Docket number 97N-0335

Description:

Intended Use:

Hyaluronidase Solution is intended for use in removing cumulus cells surrounding oocytes (denudation) in preparation for ICSI or other ART procedures.

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Technological Characteristics:

Enzymatic digestion and removal of cumulus cells surrounding freshly retrieved oocytes will occurred within a 30 - 60 second exposure to Hvaluronidase Solution. Denuded oocytes should be immediately washed and transferred to appropriate medium for subsequent fertilization (by ICSI) and onqoing development.

Performance Data:

Hyaluronidase Solution is assayed by mouse embryo assay prior to its release to market. This assay assures that the product will support embryonic growth and that no toxic components are present. The equivalent of Hyaluronidase Solution has been used in a variety of clinical settings for the same intended use for a number of years and has become the standard medium used for denuded oocytes.

Additional Information:

Mouse Embryo Assay, enzyme activity, endotoxin and sterility testing will be performed as a condition of release for this product. Results of all release assays performed will be indicated on the labeling and reported on a lot-specific certificate of analysis.

Conclusion:

The conclusion from performance testing as well as a review of the historical information contained in professional literature shows that Hyaluronidase Solution is suitable for the intended use and meets the criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/2 description: The image shows a black and white logo or emblem. The logo features a stylized depiction of what appears to be a bird in flight, represented by three curved lines that suggest movement and wings. To the left of the bird, there is a semi-circular arrangement of dots and text, which is partially obscured but seems to follow the curve of the circle. The overall design is simple yet dynamic, conveying a sense of motion and possibly representing an organization or institution.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

NOV : 4 2002

Wendall Lee, PharmD Vice President Quality Systems and Regulatory Affairs Irvine Scientific Sales Co., Inc. 2511 Daimler Street SANTA ANA CA 92705-5588

Re: K022931

Trade/Device Name: Hyaluronidase Solution Regulation Number: 21 CFR 884.6180 · Regulation Name: Reproductive media and supplements Regulatory Class: II Product Code: 85 MQL

Dated: August 23, 2002 Received: September 4, 2002

Dear Dr. Lee:

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, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (sec 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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Page 2

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), please contact the Office of Compliance at one of the following numbers, based on the regulation number at the top of this 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" (21 CFR Part 807.97). 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. Snogdon

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

Enclosure

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Irvine Scientific .

August 23, 2002

INDICATIONS FOR USE STATEMENT (page 1 of 1

KO22931 510(K) Number:

Device Name: Hyaluronidase Solution

Indications for Use:

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use_

David A. Siegmann

(Division Sign-Off) Division of Reproductive, Abd and Radiological Device 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.