V-HYADASE is intended for the enzymatic removal of cumulus and corona radiata cells from oocytes prior to intracytoplasmic sperm injection (ICSI) procedures.

Device Description

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the V-HYADASE device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Criterion	Acceptance Criteria (Subject Device, V-HYADASE)	Reported Device Performance (Implied by "met at time 0 and after accelerated aging")
Clarity/Color	Pink rose color, no precipitates	Met
pH (per USP<791>)	7.2-7.4	Met
Osmolality (per USP<785>)	257-273 mOsm/kg	Met
Endotoxin (per USP <85>)	< 0.5 EU/mL	Met
Mouse Embryo Assay (MEA)	1-Cell System: ≥80% of embryos developed to expanded blastocyst at 96h after a 4-min exposure to V-HYADASE	Met
Sterility (per USP<71>)	No growth	Met
Hyaluronidase Activity	50-120 IU/mL	Met
Shelf Life	1 Year (7 days after bottle opening)	Met

Note: The document explicitly states that the product specifications were "met at time 0 and after accelerated aging," indicating that the device performance for these criteria was within the defined acceptance limits.

Regarding the other requested information, the provided document does not contain the following details:

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

The document mentions an MEA (Mouse Embryo Assay) but does not specify the number of embryos or test repetitions used for this specific test within the context of the device's performance validation.
No information is provided about data provenance (country of origin, retrospective/prospective).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This type of information is not relevant to the non-clinical performance testing described for this device, which involves laboratory assays and physical/chemical property measurements, not expert interpretation of outputs.

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

Adjudication methods are typically associated with human-read studies or studies where subjective assessments are involved. This is not applicable to the non-clinical tests 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

No MRMC study was conducted. This device is a reproductive media, not an AI-powered diagnostic tool.

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

Standalone performance is not applicable to this device, as it is a chemical solution used in a laboratory procedure, not an algorithm.

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

The ground truth for the non-clinical tests is established by the assay parameters themselves (e.g., pH meter readings, osmolality readings, microscopic observation of embryo development according to pre-defined criteria, sterility culture results, hyaluronidase activity assays).
For the MEA, the "ground truth" is the observed development of embryos to the expanded blastocyst stage within the specified timeframe and percentage.

8. The sample size for the training set

There is no "training set" in the context of this device's non-clinical performance testing. Training sets are relevant for machine learning algorithms.

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

Not applicable, as there is no training set mentioned.

Summary of the Study that Proves the Device Meets Acceptance Criteria:

The device, V-HYADASE, underwent a series of non-clinical performance tests to demonstrate its safety and effectiveness and substantial equivalence to a predicate device (Origio A/S SynVitro Hyadase K200680). The studies included:

Sterile Filtration and Aseptic Fill Validation: Conducted per ISO 13408-1:2008 and ISO 13408-2:2018. This ensured the sterility of the final product.
Shelf-Life Testing: This was a critical study to support the claimed 12-month shelf-life and 7-day open-vial stability. The testing involved demonstrating that all the acceptance criteria listed in the table above (Clarity/Color, pH, Osmolality, Endotoxin, MEA, Sterility, Hyaluronidase Activity) were met at the initial time point (time 0) and after accelerated aging (in accordance with ASTM F1980-21). Additionally, tests were performed on aged samples that had undergone 7 days of simulated use conditioning after bottle opening to verify the open-vial stability.
Transportation Testing: Performed according to ASTM D4169-22 and USP<1207> to ensure the product's integrity during transport.

The conclusion drawn from these studies is that the "results of the performance testing described above demonstrate that V-HYADASE is as safe and effective as the predicate device and support a determination of substantial equivalence." This implies that all the stated acceptance criteria were successfully met during these non-clinical evaluations.

Summary

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May 26, 2023

VITROMED GmbH % Greg Holland Consultant Regulatory Specialists. Inc. 3722 Ave. Sausalito Irvine, CA 92606

Re: K222606

Trade/Device Name: V-HYADASE Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: April 21, 2023 Received: April 24, 2023

Dear Greg Holland:

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 -S

Monica D. Garcia, Ph.D. 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) K222606

Device Name V-HYADASE

Indications for Use (Describe)

V-HYADASE is intended for the enzymatic removal of cumulus and corona radiata cells from oocytes prior to intracytoplasmic sperm injection (ICSI) procedures.

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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510(k) Summary K222606

510(k) Owner	VITROMED GmbH
	Raiffeisenstr. 15a
	40764 Langenfeld
	Germany
	Phone: +49 2173-20041-30
	Facsimile: +49 2173-20041-58

Submission Correspondent

Greg Holland Regulatory Specialists, Inc. 3722 Ave. Sausalito Irvine, CA 92606 Phone: 949.262.0411 Fax: 949.552.2821 Email: greq@requlatoryspecialists.com

Submission Date

Regulation Number

Product Code

Class

Predicate

Trade Name Common Name Regulation Name V-HYADASE

May 23, 2023

Assisted Reproduction Media Reproductive Media and Supplements 884.6180 MQL (Media, Reproductive) Class II

Origio A/S Synvitro Hyadase K200680

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

Device Description

V-HYADASE is an assisted reproduction medium intended for the enzymatic removal of cumulus and corona radiata cells from oocyte prior to Intracytoplasmic Sperm Injection (ICSI) procedures. The medium is aseptically filtered and provided in a volume of 1 mL in pre-sterilized 2 mL polypropylene copolymer (PPCO) bottles with PPCO caps. V-HYADASE has a shelf-life of one-year when stored at 2-8°C and can be used for up to seven days after bottle opening. Additional information on the formulation and specifications of V-HYADASE are provided in the Comparison of the Subject and Predicate Device Intended Use and Technological Characteristics section of this summary.

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Indications for Use

V-HYADASE is intended for the enzymatic removal of cumulus and corona radiata cells from oocytes prior to intracytoplasmic sperm injection (ICSI) procedures.

Comparison of the Subject and Predicate Device Intended Use and Technological Characteristics

A comparison of the intended use and technological features of the subject and predicate device are described in the table below:

	Subject DeviceV-HYADASEK222606	Predicate DeviceOrigio A/SSynVitro HyadaseK200680	Comparison
Indications	V-HYADASE is intended forthe enzymatic removal ofcumulus and corona radiatacells from oocytes prior tointracytoplasmic sperminjection (ICSI) procedures.	SynVitro Hyadase is for theremoval of the cumuluscomplex and corona radiatasurrounding the occyte inpreparation for ICSI.	There are differences inthe wording of the subjectand predicate deviceindications for usestatements; however,both have the sameintended use (i.e., forremoval of cumulus andcorona radiata cells fromoocytes prior to ICSIfertilization).
Prescription UseOnly	Yes	Yes	Same
Formulation	WaterHEPESGlucose, D- (+)Calcium lactateGentamicin sulfateHSASodium BicarbonatePhysiological SaltsEssential Amino AcidsNon-Essential Amino AcidsPhenol redHyaluronidase (BovineSource)VitaminCitric AcidChelating agentSodium Pyruvate	Hyaluronidase (non-bovinesource)GlucoseSodium pyruvateCalcium chlorideMagnesium sulphateSodium chlorideHEPES	Different - The formulasof the subject andpredicate devices are notthe same. Differences inmedia formulations do notraise different questionsof safety andeffectiveness (S&E).
Sterilization	Aseptic Filtration, USP <71>- No Growth	Aseptic Filtration, USP <71>- No Growth	Same
pH	7.20-7.40	7.150-7.449	Similar
Osmolality(mOSM/kg)	257-273	272-288	Similar
Mouse EmbryoAssay (MEA)	1-Cell System: ≥80% ofembryos developed toexpanded blastocyst at 96hafter a 4-min exposure to V-HYADASE	1-Cell MEA≥80% developed within 96hours after a 15-secondexposure to SynVitroHyadase	Different - The subjectdevice specificationincludes a longerexposure of the mediumto mouse embryos. Alonger exposure does notraise different questionsof S&E.
Endotoxin (EU/ml)	<0.5	<0.5	Similar
Hyaluronidaseenzyme activity	50-120 IU/mL	40-120 IU/mL	Similar
Shelf Life	1 Year7 days (Open Vial)	1 Year7 days (Open Vial)	Same

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As shown in the table above, there are differences in the indications for use statements and technological features of the subject and predicate devices. However, the subject and predicate device have the same intended use and the differences in technological features do not raise different questions of safety and effectiveness.

Summary of Non-Clinical Performance Testing

The following studies have been performed to support substantial equivalence to the predicate device:

Sterile filtration and aseptic fill validation, per ISO 13408-1:2008 Aseptic . Processing of Health Care Products – Part 1 General Requirements (including Amendment 1 (2013)) and ISO 13408- 2:2018 – Aseptic Processing of Health Care Products - Part 2 Sterilizing Filtration.
Shelf-life testing was conducted to support the 12-month shelf-life for the subject . device through demonstration that the product specifications (shown below) were met at time 0 and after accelerated aging in accordance with ASTM F1980-21. Testing was also included on aged samples demonstrating that medium in bottles can maintain their specifications after seven days of simulated use conditioning after bottle opening. Testing conducted is shown below:
- Clarity/Color: Pink rose color, no precipitates O
- pH, per USP<791>: 7.2-7.4 O
- Osmolality, per USP<785>: 257-273 mOsm/kg O
- Endotoxin, per USP <85>: < 0.5 EU/mL O
- MEA: 1-Cell System: ≥80% of embrvos developed to expanded blastocyst o at 96h after 4-min exposure to V-HYADASE
- Sterility, per USP<71>: No growth o
- Hyaluronidase Activity: 50-120 IU/mL
Transportation testing per ASTM D4169-22 and USP<1207> ●

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Conclusions

The results of the performance testing described above demonstrate that V-HYADASE is as safe and effective as the predicate device and support 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.