VitriGuard is intended for use as a cryopreservation storage device in vitrification procedures and indicated to contain and maintain human oocytes (MII), 4-8 cell embryos and blastocyst stage embryos.

Device Description

VitriGuard is a sterile, single-use device that is intended for use as a cryopreservation storage device in vitrification procedures. The device consists of a two-piece polystyrene assembly that includes a hexagonal-shaped stick and cap. As part of the vitrification procedure, the oocytes or embryos are loaded on the tip of the stick is capped prior to plunging the device in liquid nitrogen and for subsequent storage. The tip has a trough area for loading, maintaining and securing oocytes or embryos. The stick and cap include a taper design that create a seal when assembled. Black markings at the end of the stick and the tip of the device provide visual aid for proper device orientation. All VitriGuard devices have a blue cap and the sticks are available in eight (8) translucent colors: clear, blue, green, yellow, lime green, purple, orange and pink.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study information for the VitriGuard device, based on the provided text:

VitriGuard Acceptance Criteria and Study Information

The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in a single table, but are instead derived from the "Substantial Equivalence Comparison" table and "Non-clinical performance testing" sections by comparing the subject device's performance to the predicate device and established standards. The reported device performance is also taken from these sections.

1. Table of Acceptance Criteria and Reported Device Performance

Attribute	Acceptance Criteria (typically matching predicate or standard)	Reported Device Performance (VitriGuard)
Cooling Rate	Comparable to cleared oocyte and embryo vitrification devices (Predicate: 10,000°C/min)	36,377°C/min
Warming Rate	Comparable to cleared oocyte and embryo vitrification devices (Predicate: -1,400°C/min)	-2,271°C/min
Endotoxin	≤1.0 EU/device (Predicate)	≤2.0 EU/device
MEA (1-Cell)	≥80% embryos developed to expanded blastocyst at 96h (Predicate)	≥80% embryos developed to expanded blastocyst at 96h
Sterilization SAL	10^-6^ (Predicate)	10^-6^
Number of Uses	Single-use, disposable (Predicate)	Single-use, disposable
Sterilization Method	- (Predicate: Ethylene Oxide)	Radiation
Materials	- (Predicate: PMMA, Mediprene, Stainless steel)	Polystyrene with black marker bands

Note on Acceptance Criteria: The document clearly states that differences in cooling/warming rates, endotoxin specifications, materials, and sterilization method "do not raise different questions of safety and effectiveness." This implies that while the values may differ from the predicate, they are still considered acceptable based on existing scientific understanding and relevant standards. For MEA, SAL, and number of uses, the criteria are explicitly met by matching the predicate.

2. Sample size used for the test set and the data provenance

The document indicates that clinical performance was primarily supported by a published literature review on closed-system vitrification devices similar to the subject device, rather than a single, dedicated clinical trial for VitriGuard with a specific test set.

Literature 1: 33 vitrified/warmed donated oocytes.
Literature 2: 498 vitrified/warmed donated oocytes.
Literature 3: 190 vitrified/warmed autologous oocytes.
Literature 4: Not explicitly stated as a single sample size for the study; reported on "clinical experience" with varying results based on maternal age.
Literature 5: 89 vitrified/warmed donated oocytes.
Literature 6: 33 patients, resulting in 16 embryo transfer cycles.

Data Provenance: The provenance of the data (country of origin, retrospective/prospective) is not explicitly stated for each literature reference. These are published studies by various authors (Inoue, Pujol, Perez et al, Gook et al, Pinasco et al, Goldman et al), implying they are likely a mix of prospective and retrospective observations from different clinical settings globally, based on typical scientific publication practices. The document uses this existing literature to support equivalence, rather than conducting a new, primary clinical investigation with a defined test set.

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

This information is not provided in the document. The "ground truth" for the literature review refers to outcomes measured in published clinical studies (survival rates, fertilization rates, cleavage rates, blastocyst development rates, implantation rates, pregnancy rates, live birth rates). The interpretation of these outcomes would have been performed by the researchers of those individual studies, but details on expert qualifications for establishing ground truth are not given here.

4. Adjudication method for the test set

This information is not provided in the document. Given that the clinical evidence relies on a review of published literature rather than a new, dedicated clinical study with a specific test set and adjudication panel for the VitriGuard device, no adjudication method specific to VitriGuard's clinical performance assessment is described.

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 is not applicable. The VitriGuard is a physical cryopreservation storage device, not an AI or imaging diagnostic tool that would involve "human readers" or AI assistance. Therefore, an MRMC study or assessment of AI effectiveness for human readers is irrelevant to this device.

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

This is not applicable. The VitriGuard is a physical device, and does not involve an algorithm or human-in-the-loop performance in the context of AI.

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

For the non-clinical performance testing (e.g., cooling/warming rates, endotoxin, MEA), the ground truth is established through standardized laboratory assays and measurements (e.g., USP <85> for endotoxin, ASTM standards for packaging, ISO standards for sterilization).

For the clinical evidence (literature review), the "ground truth" is derived from clinical outcomes data reported in the referenced published studies. This includes metrics such as:

Oocyte survival rates
Fertilization rates
Cleavage rates
Blastocyst development rates
Implantation rates
Clinical pregnancy rates
Live birth rates

8. The sample size for the training set

This information is not applicable. The VitriGuard is a physical medical device, not a machine learning model that requires a "training set."

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

This information is not applicable. As it's not an AI model, there is no training set or ground truth established for one.

Summary

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June 25, 2020

ORIGIO a/s % Christine Kupchick Regulatory Affairs Associate CooperSurgical, Inc. 95 Corporate Drive Trumbull, CT 06611

Re: K200815 Trade/Device Name: VitriGuard Regulation Number: 21 CFR§ 884.6160 Regulation Name: Assisted Reproduction Labware Regulatory Class: II Product Code: MQK Dated: March 27, 2020 Received: March 30, 2020

Dear Christine Kupchick:

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,

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) K200815

Device Name VitriGuard

Indications for Use (Describe)

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

Prescription Use (Part 21 CFR 801 Subpart D)

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

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a CooperSurgical company

510(k) SUMMARY K200815

Submitter Information

Company Name:	ORIGIO a/s
Company Address:	Knardrupvej 22760 Måløv Denmark
Telephone:	+ 45 46 79 02 00
Fax:	+ 45 46 79 03 02

Submission Correspondent

Company Name:	CooperSurgical Inc.
Company Address:	95 Corporate DriveTrumbull, CT 06611

Submission Contact

Name:	Christine Kupchick
Telephone:	203-601-5200 Ext. 3370
Fax:	203-601-9870
Email:	christine.kupchick@coopersurgical.com

Date Prepared: June 24, 2020

Device Identification

Trade Name:	VitriGuard
Common Name:	Cryopreservation Storage Device
Regulation Number:	21 CFR 884.6160
Regulation Name:	Assisted Reproduction Labware
Product Code:	MQK (Labware, Assisted Reproduction)
Regulatory Class:	Class II
Review Panel:	Obstetrics/Gynecology

Predicate Device Information Vitrolife Rapid-I (K181461).

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

Device Description

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the end of the stick and the tip of the device provide visual aid for proper device orientation. All VitriGuard devices have a blue cap and the sticks are available in eight (8) translucent colors: clear, blue, green, yellow, lime green, purple, orange and pink.

Indications for Use

Substantial Equivalence Discussion

The table below provides a comparison of the intended use and technological characteristics of the subject and predicate device.

Attribute	Subject VitriGuard	Predicate Rapid-I (K181461)
Indications for Use	VitriGuard is intended for use asa cryopreservation storage devicein vitrification procedures andindicated to contain and maintainhuman oocytes (MII), 4-8 cellembryos and blastocyst stageembryos.	Cryopreservation device intendedto be used to contain, vitrify andmaintain human embryos and/oroocytes (MII).
FundamentalTechnology	The device is composed of a two-piece assembly that includes astick and cap. As part of thevitrification procedure,specimens to be stored areloaded on the tip of the stick andthe stick is inserted into the pre-cooled cap to seal and to vitrifysamples for subsequent storagein LN.	The stick has a tip where thesamples are loaded. The stick issealed within a pre-cooled strawthat contains a stainless-steelweight to maintain deviceorientation in LN. The stick isinserted into the pre-cooled straw(after steel rod removal) to vitrifysamples. The end of the straw issealed, and the device is stored inLN.
Warming Rate	-2,271°C/min	-1,400°C/min
Cooling Rate	36,377°C/min	10,000°C/min
Endotoxin	≤2.0 EU/device	≤1.0 EU/device
MEA (1-Cell)	≥80% embryos developed toexpanded blastocyst at 96h	≥80% embryos developed toexpanded blastocyst at 96h
Materials	Polystyrene (clear, blue, green,yellow, orange, pink, lime green,and purple) with black markerbands	Polymethyl methacrylate (PMMA)MedipreneStainless steel
SterilizationMethod	Radiation, SAL 10-6	Ethylene Oxide, SAL 10-6
Number of Uses	Single-use, disposable	Single-use, disposable

Substantial Equivalence Comparison

The subject and predicate device have similar indications for use statements and have the same intended use – the vitrification and storage of human oocytes (MII) and embryos.

The subject and predicate device have comparable technological characteristics: samples are loaded at the tip, the stick is inserted into a pre-cooled device component, samples are vitrified, and the sealed device with the vitrified samples is placed in Liquid Nitrogen for subsequent storage. The subject device is identical to the predicate in MEA specifications, SAL, and number of uses. The subject device differs

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from the predicate in cooling/warming rates, endotoxin specifications, materials, and sterilization method, however, these differences do not raise different questions of safety and effectiveness.

Non-clinical performance testing

The following performance testing was leveraged from the original VitriGuard (K162833) to support the performance of the subject device.

. Sterilization
- Validation per ISO 11137-1:2006/(R)2010 and ISO 11137-2:2013 O
- Bioburden per ISO 11737-1:2006/(R)2011 and ISO 11737-2:2009 O
Shelf Life Testing ●
- Accelerated aging per ASTM F1980-07(2011) o
- Package Integrity Testing following accelerated aging o
  - l Dye Penetration Testing per ASTM F2096-11
  - . Seal Tensile Strength Testing per ASTM F88/F88M-15
  - . Seal Peel Testing per ASTM F1886/F1866M-09(2013)
Ship Testing per ISTA 3A:2008
Endotoxin per USP <85> and ANSI/AAMI ST72:2002/(R)2010
. Mouse Embryo Assay (MEA)
Thermal Profile Evaluation
- O Assessment of warming and cooling rates
- Comparison of warming and cooling rates to other devices cleared for oocyte and embryo O vitrification
Mouse Embryo Survival Evaluation
Mouse Embryo Development Evaluation
Container and Closure Integrity
- O Bacterial/Immersion
- O Bacterial Contaminated LN2
. Durability Testing
Product Evaluation

Published literature review

To support the use of the VitriGuard for the vitrification of MII oocytes, published literature was summarized to assess the VitriGuard, as well as other legally marketed, closed-system devices similar to the subject device in technological characteristics and indicated to contain and maintain human oocytes during vitrification procedures. A summary of the results is shown below:

Literature 1: This study evaluated the efficacy of a closed-system vitrification device for oocyte vitrification as compared to an open-system device. The results of the study show a 93.9% survival rate, 80.6% fertilization rate, 96% cleavage rate and 72% blastocyst development rate after using a closed- system device similar to the subject device. Results are based on 33 vitrified/ warmed donated oocytes using the closed-system device.2
Literature 2: This study evaluated the efficacy of a closed-system vitrification device for oocyte vitrification as compared to an open-system device. The results of the study show a 94.5% survival rate, 57.1% fertilization rate, 24.2% implantation rate, 40% clinical pregnancy rate and 37.5% live birth rate after using a closed-system vitrification device similar to the subject device.

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Results are based on 498 vitrified/warmed donated oocytes using the closed-system device, which were fertilized/ cultured and transferred to 40 recipients.2

Literature 3: This study analyzed oocyte survival rates after warming, and birth outcome of a vitrification protocol in conjunction with a closed-system device. The results of the study show a 94.2% survival rate, 80.4% fertilization rate, 95.1% cleavage rate, 36.1% blastocyst development rate, and 57.1% live birth rate after using a closed-system vitrification device similar to the subject device. Results are based on 190 vitrified/warmed autologous oocytes using the closedsystem device, which were fertilized/ cultured and transferred back to the mother (N=14). 3
Literature 4: This study reported on clinical experience after introducing a closed-system device for oocyte vitrification in daily routine. The overall results of the study show a 90.5% survival rate, 64.2% fertilization rate, 90.4% cleavage rate, 32.7% implantation rate, and 40.9% clinical pregnancy rate after using a closed-system vitrification device similar to the subject device; with results varying depending on maternal age (<38 yrs. versus ≥38 yrs.), including clinical pregnancy rates of 41.9% and 38.5% respectively. 4
Literature 5: This study evaluated the efficacy of a closed-system vitrification device for oocyte vitrification as compared to an open-system device based on donated oocytes. The results of the study show a 92.1% survival rate after using a closed-system vitrification device similar to the subject device. Results are based on 89 vitrified/ warmed donated oocytes using the closed-system device.5

1 Inoue (2014) Efficiency of a closed vitrification system with oocytes and blastocysts.

² Pujol (2019) Comparison of two different oocyte vitrification methods: a prospective, paired study on the same genetic background and stimulation protocol.

3 Perez et al (2018) Oocyte vitrification using a new vitrification medium and a new closed vitrification device. A sibling oocyte study. 4 Gook et al (2016) Closed vitrification of human oocytes and blastocysts: outcomes from a series of clinical cases.

5 Pinasco et al (2012) Oocyte vitrification freeze/thaw survival rates using an open versus closed system.

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Literature 6: This study evaluated if long-term cryopreservation (median 3.5 years storage) of human oocytes affects oocyte developmental competence, blastocyst euploidy, or live-birth rates. The results of the study show an overall 80.4% survival rate, 72.8% fertilization rate, 54.5% blastocyst development rate, 65% implantation rate, 62.5% clinical pregnancy rate and 62.5% live birth rate (including some ongoing pregnancies). Data include the use of a closedsystem vitrification device similar to the subject device. Results are based on total 33 patients ending up with 16 embryo transfer cycles.6
The published data summarized for closed-system vitrification devices similar to the subject device demonstrates the safe and effective use of the closed-system vitrification devices for oocyte cryopreservation and storage. Furthermore, a cooling/warming rate comparison demonstrates that the subject device has similar cooling/warming rates to other devices that have been cleared for oocyte vitrification and storage. Therefore, the clinical information provided above can be leveraged to demonstrate substantial equivalence to the predicate device and supports the safe and effective use of the subject device for oocyte cryopreservation and storage.

Conclusion

The results of the performance testing described above demonstrate that the VitriGuard is as safe and effective as the predicate device and supports a determination of substantial equivalence

6 Goldman et al (2015) Long-term crypreservation of human oocytes does not increase embryonic aneuploidy.

Regulation Number and Section

§ 884.6160 Assisted reproduction labware.

(a)
Identification. Assisted reproduction labware consists of laboratory equipment or supplies intended to prepare, store, manipulate, or transfer human gametes or embryos for in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), or other assisted reproduction procedures. These include syringes, IVF tissue culture dishes, IVF tissue culture plates, pipette tips, dishes, plates, and other vessels that come into physical contact with gametes, embryos or tissue culture media.(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, and clinical testing). The device, when it is a dish or plate intended for general assisted reproduction technology procedures, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.