Sydney IVF Hyaluronidase is intended for use to facilitate removal of the cumulus cells surrounding oocytes in assisted reproduction technology (ART) procedures.

Device Description

Sydney IVF Hyaluronidase is an enzymatic preparation containing 80 IU/mL Hyaluronidase (of ovine origin) in a Bicarbonate buffered media supplemented with 5 mg/mL Human Serum Albumin (HSA) and 10 ug/mL Gentamicin.

Sydney IVF Hyaluronidase is provided sterile (aseptically filtered) and is packaged in glass vials with Fluorotec coated rubber stoppers held in place with a tamper evident seal. It is available in a 5 pack carton box with each vial containing 1 mL of Sydney IVF Hvaluronidase.

AI/ML Overview

The provided text describes the Sydney IVF Hyaluronidase device and its substantial equivalence to a predicate device, focusing on its formulation, shelf-life, and performance. However, it does not contain the kind of detailed information typically found in a study demonstrating the device meets specific acceptance criteria with reported device performance against those criteria in a tabular format, nor does it provide information about the methodology of such a study (sample sizes, expert involvement, adjudication, etc.).

The document is a 510(k) summary for regulatory clearance, which primarily focuses on demonstrating substantial equivalence to a previously cleared device. It mentions "performance data" and "stability & shelf life" but doesn't present a formal study report with acceptance criteria and results in the requested format.

Therefore, I cannot fulfill your request for:

A table of acceptance criteria and the reported device performance.
Sample sizes used for the test set and data provenance.
Number of experts and their qualifications for ground truth.
Adjudication method for the test set.
MRMC comparative effectiveness study effect size.
Standalone performance.
Type of ground truth used (beyond "MEA data").
Sample size for the training set.
How ground truth for the training set was established.

However, I can extract the relevant information known about the device's performance based on the document:

The document states that the Sydney IVF Hyaluronidase (the proposed device) and the predicate device (K023353 - Sydney IVF Hyaluronidase) share similar performance specifications and that the proposed device has been validated in stability studies.

Here's what can be pieced together from your request and the provided text:

1. A table of acceptance criteria and the reported device performance:

Acceptance Criteria Category	Predicate Device Specification (K023353)	Proposed Device Performance (Sydney IVF Hyaluronidase)
Osmolality	285-295 mOsm/kg	Same (285-295 mOsm/kg)
Endotoxin	< 0.40 EU/mL	Same (< 0.40 EU/mL)
Sterility	Sterile (aseptically filtered)	Same (aseptically filtered)
Embryo Toxicity (MEA)	1-cell MEA (96hrs) with ≥75% of control that develop to blastocyst	2-cell MEA (72hrs) with ≥80% of control that develop to blastocyst
Shelf-Life	6 months at -20°C	Validated to 20 weeks at 2-8°C
Stability Tests	(Implied by predicate and proposed device sharing "performance specifications")	pH, osmolality, endotoxin, MEA, sterility, concentrations of proline, pyruvate, ammonia, and enzymatic activity of Hyaluronidase

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):

Sample Size: Not specified for any specific "test set." The document refers to "MEA data" and "stability studies" without providing sample sizes.
Data Provenance: The device is from William A. Cook Australia Pty Ltd. The "MEA data" and "stability studies" would presumably be conducted by them. The document mentions the ovine derived product has been "licensed and sold globally since 2007," and its performance is supported by "experience" during this time, suggesting real-world usage data.

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

Not specified. The "MEA data" itself serves as a performance metric, but the number or qualifications of experts involved in running or interpreting these assays are not mentioned.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not specified.

5. 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:

This device is a reproductive media and supplement (Hyaluronidase Solution), not an AI or imaging device with "human readers." Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

This is not an algorithm. The relevant "standalone performance" refers to the intrinsic performance of the chemical/biological solution, which is assessed through the MEA and stability studies.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

The primary "ground truth" or performance indicator for embryo toxicity is the Mouse Embryo Assay (MEA), which assesses the development of mouse embryos to the blastocyst stage. This is a laboratory-based, biological assay. Stability tests also involve objective measurements of chemical and physical properties (pH, osmolality, concentrations, enzymatic activity).

8. The sample size for the training set:

This concept is not applicable as this is not an AI or machine learning device that requires a "training set."

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

Not applicable (see point 8).

In summary, the document addresses regulatory clearance based on substantial equivalence, and while it references performance data (like MEA and stability studies), it does not present a detailed study report with the specific methodological details requested for evaluating AI/diagnostic devices.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains two logos. The logo on the left is the Department of Health & Human Services - USA logo. The logo on the right is the FDA U.S. Food & Drug Administration logo. The FDA logo is in blue.

November 19, 2019

William A. Cook Australia Pty Ltd Gordana Pozvek Senior Regulatory Affairs Specialist 95 Brandl Street Brisbane Technology Park, Eight Mile Plains Brisbane, OLD 4113, AUSTRALIA

Re: K151367

Trade/Device Name: Sydney IVF Hyaluronidase Regulation Number: 21 CFR 884.6180 Regulation Name: Reproductive media and supplements Regulatory Class: Class II Product Code: MOL Dated: December 15, 2015 Received: December 18, 2015

Dear Gordana Pozvek:

This letter corrects our substantially equivalent letter of January 27, 2016.

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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.

{1}------------------------------------------------

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); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Monica D. Garcia -S

Monica D. Garcia, Ph.D. Acting Assistant Director DHT3B: Division of Reproductive, Gynecology and Urology Devices OHT3: Office of Gastrorenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known)

Device Name Sydney IVF Hyaluronidase

Indications for Use (Describe)

Sydney IVF Hyaluronidase is intended for use to facilitate removal of the cumulus cells surrounding oocytes in assisted reproduction technology (ART) procedures.

Type of Use (Select one or both, as applicable)
-------------------------------------------------

|X Prescription Use (Part 21 CFR 801 Subpart D)

| | Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image shows the logo for Cook Medical. The logo is set against a red background. The word "COOK" is written in large, white, sans-serif font, with the registered trademark symbol next to it. Below "COOK", the word "MEDICAL" is written in a smaller, white, sans-serif font.

WILLIAM A. COOK AUSTRALIA PTY. LTD. 95 BRANDL STREET BRISBANE TECHNOLOGY PARK, EIGHT MILE PLAINS BRISBANE, QLD 4113, AUSTRALIA PHONE: 1800.777.222 FAX: +61.7.3841.1288 www.cookmedical.com

510(k) Summary

SUBMITTED BY:

William A. Cook Australia Pty Ltd 95 Brandl Street Eight Mile Plains OLD 4113 Australia

Contact Person:	Gordana Pozvek Ph.D.
Tel:	+61 (7) 3841 1188
Fax:	+61 (7) 3841 3905
E-mail:	Gordana.Pozvek@CookMedical.com

Date Prepared: January 26, 2016

DEVICE IDENTIFICATION:

Trade Name:	Sydney IVF Hyaluronidase (product code: K-SIHY-1-5)
Common Name:	Hyaluronidase Solution
Regulation No:	21 CFR 884.6180, Reproductive Media & Supplements
Regulatory Class:	II
Product Code:	MQL - Media, Reproductive

PREDICATE DEVICE:

K023353 - Sydney IVF Hyaluronidase (product code: K-SIHY-1-5) Date of clearance - December 20, 2002.

DEVICE DESCRIPTION:

{4}------------------------------------------------

INDICATIONS FOR USE:

Sydney IVF Hyaluronidase is intended for use to facilitate removal of the cumulus cells surrounding oocytes in assisted reproduction technology (ART) procedures.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE:

The Sydney IVF Hyaluronidase and the predicate device (K023353) have the same fundamental technology and similar technological characteristics including the following:

Similar chemical formulation
. Similar performance specifications:
- Osmolality 285 295 mOsm/kg —
- -Endotoxin < 0.40 EU/mL
- । A Mouse Embryo Assay (MEA) is used to screen the product for embryo toxicity.
Same method of sterilisation - Aseptically filtered.
Same packaging - borosilicate type 1 vials with FluroTec coated stopper and tamper evident seals

The modification that was made to the predicate device was a change in shelf-life from 6 months at -20℃ (for predicate device) to 20 weeks at 2-8℃.

The (ovine derived) Sydney IVF Hyaluronidase is functionally comparable to the (bovine derived) predicate (K023353) and shares similarity in intended use, method of use, formulation, and performance specifications.

Sydney IVF Hyaluronidase, sourced from ovine raw material certified free from the risk of BSE or other TSE forms, has been licensed and sold globally since 2007. During this time there has been no evidence that the product has been the cause of any adverse events in connection with its intended use.

Based on MEA data, and our experience with the (ovine derived) Sydney IVF Hyaluronidase marketed post-2007, this supports the safety and effectiveness of the product for its intended use. Thus the difference in technology between bovine and ovine derived material does not raise concerns regarding safety and efficacy and demonstrates that the (ovine derived) Sydney IVF Hyaluronidase is substantially equivalent to the predicate device (K023353).

PERFORMANCE DATA:

The product specifications for the Sydney IVF Hyaluronidase and the predicate device are the same regarding osmolality, sterility and endotoxin.

Bovine spongiform encephalopathy (BSE)

2 Transmissible Spongiform Encephalopathies (TSE)

{5}------------------------------------------------

Mouse Embryo Assay (MEA)

The MEA is used for both the predicate and the proposed device, but the test assay and specification has changed from 1-cell MEA (96hrs) with ≥75% of control that develop to blastocyst (predicate) to 2-cell MEA (72hrs) with ≥80% of control that develop to blastocyst. Both 1-cell and 2-cell Mouse Embryo Assays detect toxicity and test the functionality of IVF Media.

Stability & Shelf Life

The shelf-life of Sydney IVF Hyaluronidase has been validated in stability studies to 20 weeks at 2 - 8°C. Stability tests included pH, osmolality, endotoxin, MEA, sterility, the concentrations of proline (amino acid), pyruvate and the HSA by-product ammonia, and the enzymatic activity of Hyaluronidase.

CONCLUSION:

The results of the testing provide reasonable assurance that the Sydney IVF Hyaluronidase is as safe and effective as the predicate device and supports a determination of substantial equivalence.

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.