V-HYADASE

K222606 · Vitromed GmbH · MQL · May 26, 2023 · Obstetrics/Gynecology

Device Facts

• Record ID: K222606
• Device Name: V-HYADASE
• Applicant: Vitromed GmbH
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: May 26, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

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

Device Story

V-HYADASE is an assisted reproduction medium containing hyaluronidase (bovine source) used in clinical embryology laboratories. It is applied to oocytes to enzymatically digest and remove cumulus and corona radiata cells, preparing the oocyte for ICSI. The medium is provided in 1 mL volumes in polypropylene copolymer (PPCO) bottles. It is intended for use by trained embryologists. The enzymatic action facilitates the removal of surrounding cells, which is a necessary step for successful ICSI fertilization. The device is stored at 2-8°C and has a shelf-life of one year, with a seven-day stability period after opening.

Clinical Evidence

No clinical data. Substantial equivalence supported by bench testing, including sterile filtration validation (ISO 13408-1/2), shelf-life testing (ASTM F1980-21), transportation testing (ASTM D4169-22), and performance specifications (pH, osmolality, endotoxin, sterility, and MEA). MEA testing confirmed ≥80% development to expanded blastocyst at 96h after 4-minute exposure.

Technological Characteristics

Assisted reproduction medium; contains hyaluronidase (bovine), HEPES, glucose, calcium lactate, gentamicin sulfate, HSA, amino acids, phenol red, and salts. Form factor: 1 mL in 2 mL PPCO bottles. Sterilization: Aseptic filtration (USP <71>). Shelf-life: 1 year (2-8°C). Specifications: pH 7.20-7.40, osmolality 257-273 mOsm/kg, endotoxin <0.5 EU/mL, hyaluronidase activity 50-120 IU/mL.

Indications for Use

Indicated for the enzymatic removal of cumulus and corona radiata cells from oocytes prior to intracytoplasmic sperm injection (ICSI) procedures.

Regulatory Classification

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.).

Special Controls

*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.

Predicate Devices

• Origio A/S Synvitro Hyadase (K200680)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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) |
|-------------------------------------------------------------------------------------|
| <span style="font-size:100%;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) |
| <span style="font-size:100%;">☐</span> 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: [phone] |
| | Facsimile: [phone] |

Submission Correspondent

Greg Holland Regulatory Specialists, Inc. 3722 Ave. Sausalito Irvine, CA 92606 Phone: [phone] Fax: [phone] Email: [e-mail]

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 Device<br>V-HYADASE<br>K222606 | Predicate Device<br>Origio A/S<br>SynVitro Hyadase<br>K200680 | Comparison |
|----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications | V-HYADASE is intended for<br>the enzymatic removal of<br>cumulus and corona radiata<br>cells from oocytes prior to<br>intracytoplasmic sperm<br>injection (ICSI) procedures. | SynVitro Hyadase is for the<br>removal of the cumulus<br>complex and corona radiata<br>surrounding the occyte in<br>preparation for ICSI. | There are differences in<br>the wording of the subject<br>and predicate device<br>indications for use<br>statements; however,<br>both have the same<br>intended use (i.e., for<br>removal of cumulus and<br>corona radiata cells from<br>oocytes prior to ICSI<br>fertilization). |
| Prescription Use<br>Only | Yes | Yes | Same |
| Formulation | Water<br>HEPES<br>Glucose, D- (+)<br>Calcium lactate<br>Gentamicin sulfate<br>HSA<br>Sodium Bicarbonate<br>Physiological Salts<br>Essential Amino Acids<br>Non-Essential Amino Acids<br>Phenol red<br>Hyaluronidase (Bovine<br>Source)<br>Vitamin<br>Citric Acid<br>Chelating agent<br>Sodium Pyruvate | Hyaluronidase (non-bovine<br>source)<br>Glucose<br>Sodium pyruvate<br>Calcium chloride<br>Magnesium sulphate<br>Sodium chloride<br>HEPES | Different - The formulas<br>of the subject and<br>predicate devices are not<br>the same. Differences in<br>media formulations do not<br>raise different questions<br>of safety and<br>effectiveness (S&E). |
| Sterilization | Aseptic Filtration, USP <71><br>- No Growth | Aseptic Filtration, USP <71><br>- No Growth | Same |
| pH | 7.20-7.40 | 7.150-7.449 | Similar |
| Osmolality<br>(mOSM/kg) | 257-273 | 272-288 | Similar |
| Mouse Embryo<br>Assay (MEA) | 1-Cell System: ≥80% of<br>embryos developed to<br>expanded blastocyst at 96h<br>after a 4-min exposure to V-<br>HYADASE | 1-Cell MEA<br>≥80% developed within 96<br>hours after a 15-second<br>exposure to SynVitro<br>Hyadase | Different - The subject<br>device specification<br>includes a longer<br>exposure of the medium<br>to mouse embryos. A<br>longer exposure does not<br>raise different questions<br>of S&E. |
| Endotoxin (EU/ml) | <0.5 | <0.5 | Similar |
| Hyaluronidase<br>enzyme activity | 50-120 IU/mL | 40-120 IU/mL | Similar |
| Shelf Life | 1 Year<br>7 days (Open Vial) | 1 Year<br>7 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.