VitaVitro Sperm Washing Medium, VitaVitro Sperm Gradient Medium

K212410 · Shenzhen Vitavitro Biotech Co., Ltd. · MQL · Feb 1, 2022 · Obstetrics/Gynecology

Device Facts

• Record ID: K212410
• Device Name: VitaVitro Sperm Washing Medium, VitaVitro Sperm Gradient Medium
• Applicant: Shenzhen Vitavitro Biotech Co., Ltd.
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: Feb 1, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

VitaVitro® Sperm Washing Medium is intended for preparation and washing of sperm for use in assisted reproduction procedures. VitaVitro® Sperm Washing Medium is also intended for use in intrauterine insemination procedures. VitaVitro® Sperm Gradient Medium is intended for separation of motile sperm from seminal fluid for use in assisted reproduction procedures.

Device Story

VitaVitro® Sperm Washing Medium and Sperm Gradient Medium are ready-to-use solutions for sperm preparation in assisted reproduction; Sperm Washing Medium also used for intrauterine insemination. Sperm Gradient Medium utilizes silane-coated colloidal silica particles to create density gradients for separating motile sperm from seminal fluid. Solutions are aseptically filtered, packaged in PETG bottles, and stored at 2-8°C. Used in clinical laboratory settings by embryologists or trained technicians. Output is processed sperm sample for clinical use; benefits include improved sperm quality for reproductive procedures. Devices are single-use.

Clinical Evidence

Bench testing only. Performance validated via Human Sperm Survival Assay (HSSA) showing ≥ 80% control motility at 24h. Additional testing included pH, osmolality, endotoxin levels (< 0.25 EU/mL), sterility, and biocompatibility (cytotoxicity, sensitization, irritation per ISO 10993). Shelf-life supported by accelerated aging (ASTM F1980-16).

Technological Characteristics

HEPES-buffered salt solutions containing glucose, sodium lactate, sodium pyruvate, taurine, alanyl glutamine, gentamicin sulfate, and EDTA. Sperm Gradient Medium includes silane-coated colloidal silica particles. PETG bottles with HDPE closures. Sterile filtered (ISO 13408-1/2). Osmolality: 270-360 mOsm/kg depending on medium/layer. pH: 7.2-7.8. Shelf-life: 2 years. Storage: 2-8°C.

Indications for Use

Indicated for sperm preparation, washing, and separation of motile sperm from seminal fluid in assisted reproduction and intrauterine insemination 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

• SepaSperm Washing Solution (K190199)
• SepaSperm Solution (K190199)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. Food & Drug Administration".

February 1, 2022

Shenzhen VitaVitro Biotech Co., Ltd. Donghai Pan International Regulatory Specialist R601, Building B, Hai Ke Xing Tech Park, Baoshan Road No.16 Shenzhen, Guangdong 518118 China

Re: K212410

> Trade/Device Name: VitaVitro® Sperm Washing Medium, VitaVitro® Sperm Gradient Medium Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: December 16, 2021 Received: December 30, 2021

Dear Donghai Pan:

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,

For 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) K212410

#### Device Name

VitaVitro® Sperm Washing Medium, VitaVitro® Sperm Gradient Medium

Indications for Use (Describe)

Vita Vitro® Sperm Washing Medium is intended for preparation and washing of sperm for use in assisted reproduction procedures. Vita Vitro® Sperm Washing Medium is also intenderine insemination procedures.

VitaVitro® Sperm Gradient Medium is intended for separation of motile sperm from seminal fluid for use in assisted reproduction 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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Image /page/3/Picture/0 description: The image shows the logo for VitaVitro. The logo consists of a stylized green checkmark-like symbol with three rounded points. To the right of the symbol is the text "VitaVitro" in a sans-serif font, also in green. The logo is simple and modern, likely representing the company's name and brand identity.

# 510(k) SUMMARY K212410

# 1. Submission Sponsor

Shenzhen VitaVitro Biotech Co., Ltd. R601, Building B, Hai Ke Xing Tech Park Baoshan Road No. 16 Shenzhen 518118 Guangdong China Contract Person: Mr. Donghai Pan Title: International Regulatory Specialist Tel: [phone] Fax: [phone] Email: [e-mail]

# 2. Date Prepared

January 26, 2022

#### 3. Device Identification

| Trade Name: | VitaVitro® Sperm Washing Medium, VitaVitro® Sperm Gradient Medium |
|--------------------|-------------------------------------------------------------------|
| Common Name: | Sperm Washing Medium, Sperm Gradient Medium |
| Regulation Number: | 21 CFR 884.6180 |
| Regulation Name: | Reproductive Media and Supplements |
| Regulatory Class: | Class II |
| Product Code: | MQL (Media, Reproductive) |

# 4. Predicate Device

# Table 1. Predicate Devices

| Subject Devices | VitaVitro® Sperm Washing Medium | VitaVitro® Sperm Gradient Medium | |
|----------------------|---------------------------------|----------------------------------|--------------------|
| Predicate<br>Devices | Trade Name | SepaSperm Washing Solution | SepaSperm Solution |
| | Manufacturer | Kitazato Corporation | |
| | 510(k) No. | K190199 | |
| | Regulatory Class | Class II | |
| | Product Code | MQL (Media, Reproductive) | |

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The predicate devices have not been subject to any design-related recalls.

#### 5. Device Description

VitaVitro® Sperm Washing Medium and VitaVitro® Sperm Gradient Medium are ready-to-use solutions intended for preparing sperm for use in assisted reproductive procedures:

- VitaVitro® Sperm Washing Medium is for sperm washing and for intrauterine insemination procedures.
- VitaVitro® Sperm Gradient Medium is for sperm density-gradient centrifugation and separation from seminal fluid.

Both devices have a similar base formulation; however, the VitaVitro® Sperm Gradient Medium formulation differs as it contains silane silica and does not contain Human Serum Albumin (HSA). The silane silica in the VitaVitro® Sperm Gradient Medium (upper layer 80%) generates the density gradient for sperm separation procedures.

The subject devices are aseptically filtered, colorless solutions, contained in transparent and sterilized (gamma irradiation) polyethylene terephthalate glycol (PETG) bottles, sealed with high density polyethylene (HDPE) closures, provided in cardboard boxes, individually labeled and with an instruction for use provided as a package insert.

The devices are provided in the following volumes:

- VitaVitro® Sperm Washing Medium: 30mL, 60mL, and 125mL
- VitaVitro® Sperm Gradient Medium: 12mL, 30mL, and 125mL

Both devices have a two-year shelf-life when stored as recommended. These devices are for single-used only.

### 6. Indications for Use

| No. | Device Name | Indications for Use |
|-----|-------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 1 | VitaVitro® Sperm<br>Washing Medium | VitaVitro® Sperm Washing Medium is intended for preparation and washing of<br>sperm for use in assisted reproduction procedures. VitaVitro® Sperm Washing<br>Medium is also intended for use in intrauterine insemination procedures. |
| 2 | VitaVitro® Sperm<br>Gradient Medium | VitaVitro® Sperm Gradient Medium is intended for separation of motile sperm from<br>seminal fluid for use in assisted reproduction procedures. |

#### Table 2. Indications for Use

#### 7. Comparison of intended use and technological characteristics of the subject and predicate devices

The table below provides comparisons of the intended use and technological characteristics of the subject and predicate devices.

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| Parameters for<br>comparison | Subject Devices<br>VitaVitro® Sperm Washing<br>Medium, VitaVitro® Sperm<br>Gradient Medium | Predicate Devices<br>SepaSperm Washing Solution,<br>SepaSperm Washing Solution | Comparison |
|------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for<br>Use | VitaVitro® Sperm Washing Medium<br>is intended for preparation and<br>washing of sperm for use in<br>assisted reproduction procedures.<br>VitaVitro® Sperm Washing Medium<br>is also intended for use in<br>intrauterine insemination<br>procedures.<br><br>VitaVitro® Sperm Gradient Medium<br>is intended for separation of motile<br>sperm from seminal fluid for use in<br>assisted reproduction procedures. | SepaSperm Washing Solution is<br>used for preparation and washing<br>of sperm for use in assisted<br>reproduction procedures.<br>SepaSperm Washing Solution is<br>not intended for use in<br>intrauterine insemination<br>procedures.<br><br>SepaSperm Solution is used for<br>separation of motile sperm from<br>seminal fluid for use in assisted<br>reproduction procedures. | The indications for use<br>statements for the<br>VitaVitro® Sperm Washing<br>Medium and the<br>SepaSperm Washing<br>Solution are not identical,<br>as the VitaVitro® Sperm<br>Washing Medium can also<br>be used for intrauterine<br>insemination (IUI)<br>procedures. The use for IUI<br>procedures represents an<br>additional use of the<br>VitaVitro® Sperm Washing<br>Medium, but does not<br>represent a new intended<br>use (i.e., washing and<br>preparing sperm for use in<br>assisted reproduction<br>procedures).<br><br>The indications for use and<br>intended use of the<br>VitaVitro® Sperm Gradient<br>Medium and the<br>SepaSperm Solution are<br>the same. |
| Device<br>Materials | HEPES Buffered Salt Solution;<br>Glucose;<br>Sodium Lactate;<br>Sodium Pyruvate;<br>Taurine;<br>Alanyl Glutamine;<br>Gentamicin Sulfate;<br>EDTA;<br>Water;<br>Human Serum Albumin (VitaVitro®<br>Sperm Washing Medium only);<br>Silane-coated Colloidal Silica<br>Particles (VitaVitro® Sperm<br>Gradient Medium only) | HEPES Buffered Salt Solution;<br>D-glucose;<br>Dextran;<br>Polyvinylpyrrolidone;<br>Gentamicin (with or without);<br>Water;<br>Silica (SepaSperm Solution only) | Different: The<br>formulations and volume<br>of the subject and<br>predicate devices are not<br>identical. Differences in<br>media product<br>formulations and volume<br>do not raise different<br>questions of safety and<br>effectiveness (S&E). |
| Packaging | 30mL, 60mL, 125mL bottle | 50mL, 100mL bottle | |
| Sterility | No microbial growth | No microbial growth | Same |
| Osmolality | VitaVitro® Sperm Washing<br>Medium: 270-300 mOsm/kg<br><br>VitaVitro® Sperm Gradient<br>Medium: | 270-300 mOsm/kg | Different: The osmolality<br>of the VitaVitro® Sperm<br>Gradient Medium is higher<br>than the predicate.<br>Differences in media |

| | Table 3. Comparison Between Subject and Predicate Devices | |
|--|-----------------------------------------------------------|--|

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| Parameters for<br>comparison | Subject Devices<br>VitaVitro® Sperm Washing<br>Medium, VitaVitro® Sperm<br>Gradient Medium | Predicate Devices<br>SepaSperm Washing Solution,<br>SepaSperm Washing Solution | Comparison |
|-----------------------------------------|---------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Upper layer 40%: 270-330<br>mOsm/kg<br>Lower layer 80%: 300-360<br>mOsm/kg | | osmolality do not raise<br>different questions of S&E. |
| pH | VitaVitro® Sperm Washing<br>Medium: 7.2-7.6<br>VitaVitro® Sperm Gradient<br>Medium: 7.4-7.8 | 7.2-7.6 | Similar |
| Human Sperm<br>Survival Assay<br>(HSSA) | ≥ 80% of control motility at 24h | ≥ 80% of control motility at 24h | Same |
| Endotoxin | < 0.25 EU/mL | < 0.25 EU/mL | Same |
| Storage<br>Temperature | 2 - 8°C | 2 - 8°C | Same |
| Shelf-life | 2 years | 1 year (with gentamicin) | Different: The shelf-life of<br>the subject and predicate<br>devices is not the same.<br>Differences in shelf-life do<br>not raise different<br>questions of S&E. |

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, as stated in the differences in indications for use do not represent a new intended use and the differences in technological features do not raise different questions of safety and effectiveness.

#### 8. Summary of Non-Clinical Performance

The following studies have been performed to support substantial equivalence to the predicate devices. Results confirm that the design inputs and performance specifications for the device are met.

| Specification | VitaVitro® Sperm Washing Medium | VitaVitro® Sperm Gradient Medium |
|--------------------------------------|----------------------------------|----------------------------------------------------------------------|
| Specific gravity (per USP <841>) | N/A | Lower layer 80%: 1.10±0.03 g/mL<br>Upper layer 40%: 1.05±0.03 g/mL |
| pH (per USP <791>) | 7.2 - 7.6 | 7.4 - 7.8 |
| Osmolality (per USP <785>) | 270-300 mOsm/kg | Lower layer 80%: 300-360 mOsm/kg<br>Upper layer 40%: 270-330 mOsm/kg |
| Endotoxin (per USP <85>) | < 0.25 EU/mL | < 0.25 EU/mL |
| Human Sperm Survival Assay<br>(HSSA) | ≥ 80% of control motility at 24h | ≥ 80% of control motility at 24h |

### Table 4. Device Specifications

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| Sterility (per USP <71>) | No microbial growth | No microbial growth |
|--------------------------|---------------------|---------------------|
|--------------------------|---------------------|---------------------|

- Sterile filtration and aseptic fill validation, per ISO 13408-1:2008 (Aseptic processing of health care products - Part 1: General requirements) and ISO 13408-2:2018 (Aseptic processing of health care products - Part 2: Sterilizing filtration).
- · Transportation testing per ASTM D4169-16 (Standard Practice for Performance Testing of Shipping Containers and Systems).
- Shelf-life testing to support the two-year shelf-life by demonstrating that the product specifications listed in Table 4 were met at time 0 and after accelerated aging in accordance with ASTM F1980-16.
- Biocompatibility testing was conducted in support of the VitaVitro® Sperm Washing Medium that will have direct contact with the patient during IUI procedures. Testing was conducted in accordance with the 2020 FDA guidance document "Use of International Standard ISO 10993-1, Biological Evaluation of Medical Devices – Part 1: Evaluation and testing within a risk management process." Testing included:
- Cytotoxicity per ISO 10993-5: 2009 o
- Sensitization per ISO 10993-10: 2010 o
- O Irritation per ISO 10993-10: 2010

The testing demonstrated the device formulation to be non-cytotoxic, non-sensitizing, and non-irritating.

- Sperm assessment for motility, morphology, viability, and purity before and after separation procedures using VitaVitro® Sperm Gradient Medium to assess the effectiveness of the device when used as intended.
# 9. Conclusion

The results of the performance testing described above demonstrate that the subject media products are as safe and effective as the predicate devices and support a determination of substantial equivalence.