SynVitro® Hyadase is a modified version of the prior cleared SynVitro® Hyadase device and is used for removal of cumulus and corona radiata cells surrounding the oocytes (denudation) prior to intracytoplasmic sperm injection (ICSI).

SynVitro® Hyadase is a clear non-viscous hyaluronidase enzyme solution contained in a 2 ml transparent plastic bottles (containing 1 ml solution) with caps and provided in cardboard boxes containing five bottles. This product has a one-year shelf-life when stored as recommended and can be used for up to seven days after opening.

AI/ML Overview

This document describes the acceptance criteria and the study that demonstrates the performance of the SynVitro® Hyadase device.

1. Table of Acceptance Criteria and Reported Device Performance

Test	Acceptance Criterion	Reported Device Performance
pH	7.150 - 7.449	Met (tested at time zero, end of shelf-life (52 weeks), and after seven days of simulated vial opening)
Osmolality	272 - 288 mOsm/kg	Met (tested at time zero, end of shelf-life (52 weeks), and after seven days of simulated vial opening)
Sterility	No growth	Met (tested at time zero, end of shelf-life (52 weeks), and after seven days of simulated vial opening)
Endotoxin	≤ 0.5 EU/ml	Met (tested at time zero, end of shelf-life (52 weeks), and after seven days of simulated vial opening)
Mouse Embryo Assay (MEA)	≥ 80% of one-cell stage embryos developed to blastocyst stage within 96 hours after a 15-second exposure to SynVitro® Hyadase	Met (tested at time zero, end of shelf-life (52 weeks), and after seven days of simulated vial opening). For a valid assay, at least 80% of one-cell stage control embryos developed to blastocyst stage within 96 hours.
Hyaluronidase enzyme activity	40 - 120 IU/ml	Met (tested at time zero, end of shelf-life (52 weeks), and after seven days of simulated vial opening). The device is specified to contain 80 IU/ml.
Aseptic Processing Validation	Compliance with ISO 13408-1:2008 and ISO 13408-2:2018	Report indicates "conducted per" the standards, implying compliance.
Shelf-Life	52 weeks (unopened vial) and 7 days (open vial)	The shelf-life testing was conducted to ensure all product specifications (pH, Osmolality, One-cell MEA, Endotoxin concentration, Sterility testing, Hyaluronidase activity) are met at time zero, at the end of the 52-week shelf-life, and after seven days of simulated vial opening. The document concludes that "performance data demonstrate that the subject device is substantially equivalent to the predicate device," implying these criteria were met.

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

The document does not explicitly state the specific "sample size" for each test in terms of number of units or replicates. For the Mouse Embryo Assay (MEA), the acceptance criterion mentions "at least 80% of the one-cell stage control embryos" which implies a set of embryos were used, but the exact number is not provided.

The data provenance is not specified. It is likely internal testing conducted by ORIGIO a/s, a CooperSurgical Company, given they are the manufacturer and submitter of the 510(k). The document does not indicate country of origin for data or if it was retrospective or prospective.

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

This document describes the testing of a medical device (reproductive media) against established physical, chemical, and biological performance specifications, not an AI or diagnostic device that requires expert adjudication of images or clinical data. Therefore, the concept of "experts used to establish the ground truth" in the context of image interpretation or clinical diagnosis does not apply here. The "ground truth" for each test is the established scientific/regulatory standard or a biological outcome (e.g., embryo development to blastocyst stage).

4. Adjudication Method for the Test Set

Not applicable. As explained in point 3, this is not a study requiring expert adjudication of data or images. The tests described are laboratory analyses with objective endpoints.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This device is a reproductive media (hyaluronidase enzyme solution) and not a diagnostic or AI-assisted interpretation device that would involve human readers.

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

No, this is not an algorithm or AI-based device. The device itself is a chemical solution. The performance testing is a standalone evaluation of the solution's properties and efficacy as intended.

7. The Type of Ground Truth Used

The ground truth used for the tests is based on:

Established scientific/regulatory standards: For pH (USP <791>), Osmolality (USP <785>), Sterility (USP <71>), and Endotoxin (USP <85>). Aseptic processing validation adheres to ISO standards.
Biological efficacy defined by a specific outcome: For the Mouse Embryo Assay (MEA), the ground truth is the development of one-cell mouse embryos to the blastocyst stage within 96 hours.
Quantitative measurement of active ingredient: For Hyaluronidase enzyme activity, the ground truth is the measured activity falling within a specified range (40-120 IU/ml), with the device specified at 80 IU/ml.

8. The Sample Size for the Training Set

Not applicable. This is not an AI or machine learning device that requires a "training set." The performance testing described evaluates the chemical and biological properties of the manufactured product.

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

Not applicable. Same as point 8.

Summary

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July 17, 2020

Origio a/s, a CooperSurgical Company Monika Bak, Ph.D. Regulatory Affairs Officer Knardrupvej 2 Måløv 2760 Denmark

Re: K200680

Trade/Device Name: SynVitro® Hyadase Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: June 11, 2020 Received: June 19, 2020

Dear Monika Bak:

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.

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.

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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-regulatoryinformation/postmarketing-safety-reporting-combination-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,

For 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

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Indications for Use

510(k) Number (if known) K200680

Device Name SynVitro® Hyadase

Indications for Use (Describe) SynVitro® Hyadase is for the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI.

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)

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510(k) SUMMARY

K200680 - SynVitro® Hyadase

510(k) SUBMITTER
Company Name:	ORIGIO a/s
Company Address:	Knardrupvej 22760 Måløv,Denmark
CONTACT
Name:	Monika Bak, PhD
Telephone:	+45 60190206
Fax:	+45 4679 0300
E-mail:	monika.bak@coopersurgical.com

Date Prepared: July 15, 2020

Device Identification

Trade name:	SynVitro® Hyadase
Common Name:	Reproductive Media
Regulation Number:	21 CFR 884.6180
Regulation Name:	Reproductive Media and Supplements
Product Code:	MQL (Media, Reproductive)
Regulatory Class:	Class II

Predicate Device Information

K031228 - SynVitro Hyadase

The predicate device has not been subject to a design-related recall.

Device Description

Indications for Use

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

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Table 1: Substantial Equivalence Comparison

Attribute	K200680Subject Device:SynVitro® Hyadase	K031228Predicate Device:SynVitro® Hyadase	Comparison
Manufacturer	ORIGIO a/s	ORIGIO a/s(formerly MediCult a/s)	Same
Indications for Use	SynVitro® Hyadase is for the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI.	For the removal of the cumulus complex and corona radiata surrounding the oocyte in preparation for ICSI.	Same
Product Design	Clear non-viscous solution contained in 2 ml transparent plastic bottles (containing 1 ml solution) with caps, with five bottles provided per box.	Clear non-viscous solution contained in 2 ml transparent plastic bottles (containing 1 ml solution) with caps, with five bottles provided per box.	Same
Formulation	Hyaluronidase 80 IU/ml (non-bovine source) Glucose Sodium pyruvate Calcium chloride Magnesium sulphate Sodium chloride HEPES	Hyaluronidase 80 IU/ml (non-bovine source) ART supplement Glucose Sodium pyruvate Calcium chloride Magnesium sulphate Sodium chloride Sodium bicarbonate HEPES	Different
pH	7.150-7.449	7.150-7.449	Same
Osmolality	272-288 mOsm/kg	272-288 mOsm/kg	Same
Endotoxin	≤0.5 EU/ml	Meets requirements per USP	Different
Hyaluronidase activity	80 IU/ml	80 IU/ml	Same
Mouse Embryo Assay	One-cell: ≥80% developed to the blastocyst stage within 96 hours after a 15-second exposure to SynVitro® Hyadase	One-cell: ≥80% developed to the blastocyst stage within 96 hours after a 15-second exposure to SynVitro® Hyadase	Same
Shelf Life	7 days (Open Vial)52 weeks shelf life	Single use (Open vial)15 weeks shelf life	Different

The subject and predicate devices have the same indications for use/intended use for removal of cumulus complex and corona radiata cells surrounding the oocyte in preparation for ICSI. In addition, the subject and predicate devices have the same hyaluronidase activity and specifications for pH, mouse embryo assay (MEA), and osmolality. However, differences exist in formulation,

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endotoxin, and device shelf-life. These differences do not raise different questions of safety and effectiveness as compared to the predicate device.

Non-Clinical Performance Testing

As part of demonstrating substantial equivalence to the predicate, a risk analysis was completed to identify the risks associated with the SynVitro® Hyadase formulation changes and shelf life claims. Verification testing was conducted to evaluate the modifications. The following tests associated with the device modifications were performed on the subject device according to methods and acceptance criteria outlined in the predicate device (K031228):

pH testing was conducted per USP <791> (acceptance criterion: pH 7.150-7.449)
Osmolality testing was conducted per USP <785> (acceptance criterion: 272-288 mOsm/kg)
Aseptic Processing Validation was conducted per ISO 13408-1:2008 and ISO 13408-2:2018 ●
Sterility testing was conducted per USP <71> (acceptance criterion: no growth)
Endotoxin testing was conducted per USP <85> (acceptance criterion: ≤ 0.5 EU/ml)
Mouse embryo assay (MEA): One-cell mouse embryos were exposed to test article for 15 seconds, followed by a 96-hr culture. For a valid assay it is required that at least 80% of the one-cell stage control embryos develop to blastocysts stage within 96 hours. (acceptance criterion: One-cell: ≥80% developed to the blastocyst stage within 96 hours after a 15second exposure to SynVitro® Hyadase)
Hyaluronidase enzyme activity – measured by incubation of SynVitro® Hyadase with hyaluronic acid and assessment of turbidity of the resulting sample using a spectrophotometer at 640 nm. (acceptance criterion: 40-120 IU/ml)
. Shelf-life testing was conducted to ensure that the following product specifications are met at time zero, at the end of the shelf-life (52 weeks), and after seven days of simulated vial opening:
- pH
- -Osmolality
- One-cell MEA -
- -Endotoxin concentration
- -Sterility testing
- -Hyaluronidase activity

Conclusion

The subject and predicate device have the same intended use and comparable technological characteristics. The differences in technological characteristics between the subject and predicate devices do not raise different questions of safety and effectiveness. The performance data demonstrate that the subject device is substantially equivalent to the predicate device.

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.