Gx-IVF, Gx-TL, Gx-MOPS PLUS

K202862 · Vitrolife Sweden AB · MQL · May 14, 2021 · Obstetrics/Gynecology

Device Facts

• Record ID: K202862
• Device Name: Gx-IVF, Gx-TL, Gx-MOPS PLUS
• Applicant: Vitrolife Sweden AB
• Product Code: MQL · Obstetrics/Gynecology
• Decision Date: May 14, 2021
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 884.6180
• Device Class: Class 2

Intended Use

Gx-IVF™ medium is intended for preparation and handling of gametes, for in vitro fertilisation and intrauterine insemination. Gx-TL™ medium is intended for culture of embryos from fertilisation to the blastocyst stage and for embryo transfer. Gx-MOPS™ PLUS medium is intended for handling and manipulating oocytes and embryos in ambient atmosphere.

Device Story

Gx-IVF, Gx-TL, and Gx-MOPS PLUS are reproductive media used in ART procedures. These liquid media contain physiological salts, energy substrates, amino acids, buffering agents, nutrients, antioxidants, gentamicin, and human serum albumin. IVF professionals use these media in clinical settings to support gamete handling, embryo culture from fertilization to blastocyst stage, and embryo transfer. Gx-MOPS PLUS is specifically formulated for manipulation in ambient atmosphere. The media are supplied in gamma-sterilized PETG bottles. By providing a controlled chemical environment, these media facilitate successful fertilization and embryo development, directly supporting clinical decision-making regarding embryo selection and transfer, ultimately benefiting patients undergoing fertility treatments.

Clinical Evidence

Bench testing only. Performance validated via aseptic filling validation (ISO 13408), sterility (USP <71>), bacterial endotoxins (USP <85>), pH (USP <791>), osmolality (USP <785>), and Mouse Embryo Assay (MEA) (acceptance: ≥80% development to expanded blastocyst at 96 hours). Shelf-life, open/close stability, and transportation (ASTM D4169-16) testing performed. Biocompatibility confirmed via cytotoxicity (ISO 10993-5) and irritation/sensitization (ISO 10993-10).

Technological Characteristics

Media consist of physiological salts, energy substrates, amino acids, buffering agents (sodium bicarbonate or MOPS), nutrients, antioxidants, gentamicin, and human serum albumin. Aseptically filtered into gamma-sterilized PETG bottles with HDPE closures. Specifications include pH (7.27-7.30), osmolality (261-270 mOsm/kg), and endotoxin levels <0.25 EU/mL. Storage at +2 to +8°C.

Indications for Use

Indicated for use in Assisted Reproduction Technology (ART) procedures, specifically for the preparation, handling, and culture of gametes, oocytes, and embryos, and for intrauterine insemination.

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

• G-IVF PLUS (K081116)
• G-TL (K133568)
• G-MOPS PLUS (K081115)

Submission Summary (Full Text)

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May 14, 2021

Vitrolife Sweden AB Sarah Hood Hagberg Regulatory Affairs Manager Gustaf Werners gata 2 Västra Frölunda. 42132 Sweden

Re: K202862

Trade/Device Name: Gx-IVFTM, Gx-TLTM, Gx-MOPSTM PLUS Regulation Number: 21 CFR§ 884.6180 Regulation Name: Reproductive Media and Supplements Regulatory Class: II Product Code: MQL Dated: April 6, 2021 Received: April 8, 2021

Dear Sarah Hood Hagberg:

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/cdrl-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, 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) K202862

Device Name Gx-IVF™, Gx-TL™, Gx-MOPSTM PLUS

#### Indications for Use (Describe)

Gx-IVF™ medium is intended for preparation and handling of gametes, for in vitro fertilisation and intrauterine insemination.

Gx-TL™ medium is intended for culture of embryos from fertilisation to the blastocyst stage and for embryo transfer.

Gx-MOPS™ PLUS medium is intended for handling and manipulating oocytes and embryos in ambient atmosphere.

| Type of Use (Select one or both, as applicable) |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| <div> <span> <svg fill="none" height="16" viewbox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"> <path d="M13.6569 2.34315C14.299 2.98529 14.299 3.99997 13.6569 4.64211L4.64211 13.6569C3.99997 14.299 2.98529 14.299 2.34315 13.6569C1.69924 13.013 1.69924 11.9983 2.34315 11.3562L11.3569 2.34211C12.0009 1.69905 13.0156 1.69905 13.6569 2.34315Z" fill="black"></path> <path d="M2.34315 2.34315C2.98529 1.69905 3.99997 1.69905 4.64211 2.34315L13.6569 11.3569C14.299 11.999 14.299 13.0137 13.6569 13.6569C13.013 14.299 11.9983 14.299 11.3562 13.6569L2.34211 4.64211C1.69905 3.99905 1.69905 2.98437 2.34315 2.34315Z" fill="black"></path> </svg> </span> Prescription Use (Part 21 CFR 801 Subpart D) </div> |
| <div> <span> <svg fill="none" height="16" viewbox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"> <rect height="15" rx="1.5" stroke="black" width="15" x="0.5" y="0.5"></rect> </svg> </span> Over-The-Counter Use (21 CFR 801 Subpart C) </div> |

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# 510(k) Summary – K202862

# 1. Submitter Information

| Submitted by: | Vitrolife Sweden AB<br>Gustaf Werners gata 2<br>SE - 421 32 Västra Frölunda<br>Sweden |
|--------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | Sarah Hood Hagberg<br>Vitrolife Sweden AB<br>Gustaf Werners gata 2<br>SE - 421 32 Västra Frölunda<br>Sweden<br>Phone: [phone]<br>Fax: [phone]<br>Email: [e-mail] |
| 2. Date Prepared: | May 11, 2021 |
| 3. Device Identification | |
| Trade Name: | Gx-IVFTM, Gx-TLTM, Gx-MOPSTM PLUS |
| Common Name: | IVF handling medium, embryo culture medium, IVF transfer medium |
| Regulatory Class: | Class II |
| Regulation Number: | 21 CFR 884.6180 |
| Regulation Name: | Reproductive Media and Supplements |
| Product Code: | MQL (Media, Reproductive) |
| 4. Predicate Device(s): | G-IVFTM PLUS (K081116) manufactured by Vitrolife Sweden AB |
| | G-TLTM (K133568) manufactured by Vitrolife Sweden AB |
| | G-MOPSTM PLUS (K081115) manufactured by Vitrolife<br>Sweden AB |

The predicate devices have not been subject to a design related recall.

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# 5. Device Description

The subject devices are culture and handling media consisting of physiological salts, energy substrates, amino acids, buffering agents, nutrients supplements, antioxidants, gentamicin and human serum albumin. These devices have different applications in Assisted Reproduction Technology (ART) procedures handled by IVF professionals, as follows:

- . Gx-IVF™ medium is intended for preparation and handling of gametes, for in vitro fertilisation and intrauterine insemination.
- . Gx-TL™ medium is intended for culture of embryos from fertilisation to the blastocyst stage and for embryo transfer.
- . Gx-MOPS™ PLUS medium is intended for handling and manipulating oocytes and embryos in ambient atmosphere.

The media are aseptically filtered into gamma sterilised PETG bottles with HDPE closure and a tamper evident seal and tested for pH, osmolality, embryo toxicity, endotoxins, and sterility.

| Device | Indications for Use |
|----------------|-----------------------------------------------------------------------------------------------------------------------------------|
| Gx-IVFTM | Gx-IVFTM medium is intended for preparation and handling of<br>gametes, for in vitro fertilisation and intrauterine insemination. |
| Gx-TLTM | Gx-TLTM medium is intended for culture of embryos from<br>fertilisation to the blastocyst stage and for embryo transfer. |
| Gx-MOPSTM PLUS | Gx-MOPSTM PLUS medium is intended for handling and<br>manipulating oocytes and embryos in ambient atmosphere. |

## 6. Indications for Use

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

| Device | Subject Device | Predicate Device (K081116) |
|-----------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------|
| Trade name | Gx-IVFTM | G-IVFTM PLUS |
| Indications for Use | Gx-IVFTM medium is intended<br>for preparation and handling of<br>gametes, for in vitro<br>fertilisation and intrauterine<br>insemination. | Medium for preparation and<br>handling of gametes, for in<br>vitro fertilization. |
| | Composition | |
| Antibiotics | Gentamicin | Gentamicin |
| Protein | Human Serum Albumin | Human Serum Albumin |
| Amino acids | YES | YES |
| Glucose | YES | YES |
| Physiological<br>salts | YES | YES |
| Buffer | Sodium bicarbonate | Sodium bicarbonate |
| | Product and performance specification | |
| pH | 7.30 ± 0.10 | 7.30 ± 0.10 |
| Osmolality (mOsm/kg) | 265 ± 5 | 262 ± 5 |
| Bacterial endotoxin<br>(LAL assay) [IU or<br>EU/mL] | < 0.25 | < 0.25 |
| Sterility | No evidence of microbial<br>growth | SAL 10-3 |
| Mouse Embryo Assay<br>(MEA) | 1-cell: ≥ 80% embryos<br>developed to expanded<br>blastocyst at 96 hours | 1-cell MEA % Expanded<br>blastocyst on day 5:<br>≥ 80 |
| Sterilization method | Aseptic filtration | Aseptic filtration |
| Storage conditions | Store dark at +2 to +8°C | Store dark at +2 to +8°C |
| Bottle | Nalgene PETG bottle with<br>HDPE closure and tamper<br>evident seal | Nalgene PETG bottle with<br>HDPE closure and tamper<br>evident seal |

The subject and predicate devices have similar Indications for Use and have the same intended use, as both the subject device and the predicate device are intended for use in ART procedures.

The subject and predicate device have different technological features, including different ingredients and specifications. The different technological characteristics, including composition and specifications, do not raise different questions of safety and effectiveness.

| Device | Subject Device | Predicate device |
|---------------------|----------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------|
| | | (K133568) |
| Trade name | Gx-TLTM | G-TLTM |
| Indications for Use | Gx-TLTM medium is intended<br>for culture of embryos from<br>fertilisation to the blastocyst | Medium for culture of<br>embryos from fertilisation to<br>the blastocyst stage |

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| | stage and for embryo transfer. | |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------|---------------------------------------------------------------|
| | Composition | |
| Antibiotics | Gentamicin | Gentamicin |
| Protein | Human Serum Albumin | Human Serum Albumin |
| Amino acids | Yes | Yes |
| Glucose | Yes | Yes |
| Hyaluronan | Yes | Yes |
| Physiological salts | Yes | Yes |
| Buffer | Sodium bicarbonate | Sodium bicarbonate |
| | Product and performance specification | |
| pH | $7.27 \pm 0.07$ | $7.30 \pm 0.10$ |
| Osmolality (mOsm/kg) | $265 \pm 5$ | $270 \pm 5$ |
| Bacterial endotoxin (LAL assay) [IU or EU/mL] | < 0.25 | < 0.25 |
| Sterility | No evidence of microbial growth | SAL 10-3 |
| Mouse Embryo Assay (MEA) | 1-cell: ≥ 80% embryos developed to expanded blastocyst at 96 hours | 1-cell MEA % Expanded blastocyst within 96 hours: > 80 |
| Sterilization method | Aseptic filtration | Aseptic filtration |
| Storage conditions | Store dark at +2 to +8°C | Store dark at +2 to +8°C |
| Bottle | Nalgene PETG bottle with HDPE closure and tamper evident seal | Nalgene PETG bottle with HDPE closure and tamper evident seal |
| The subject and predicate device have similar Indications for Use and the same intended use, as both the subject device and the predicate device are intended for use in ART procedures | | |
| The subject and predicate device have different technological features, including different ingredients and specifications. The different technological characteristics, including composition and specifications, do not raise different questions of safety and effectiveness. | | |

| Device | Subject Device | Predicate device |
|---------------------------------------|----------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|
| | | (K081115) |
| Trade name | Gx-MOPS™ PLUS | G-MOPS™ PLUS |
| Indications for Use | Gx-MOPS™ PLUS medium is<br>intended for handling and<br>manipulating oocytes and<br>embryos in ambient<br>atmosphere | Medium for handling and<br>manipulating oocytes and<br>embryos in ambient atmosphere |
| Composition | | |
| Antibiotics | Gentamicin | Gentamicin |
| Protein | Human Serum Albumin | Human Serum Albumin |
| Amino acids | Yes | Yes |
| Glucose | Yes | Yes |
| Physiological salts | Yes | Yes |
| Buffer | MOPS | MOPS |
| Product and performance specification | | |
| pH | 7.27 ± 0.07 | 7.27 ± 0.07 |
| Osmolality (mOsm/kg) | 265 ± 5 | 261 ± 5 |

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| Bacterial endotoxin<br>(LAL assay) [IU or<br>EU/mL] | < 0.25 | < 0.25 |
|-----------------------------------------------------|--------------------------------------------------------------------------|---------------------------------------------------------------------|
| Sterility | No evidence of microbial<br>growth | SAL 10-3 |
| Mouse Embryo Assay<br>(MEA) | 1-cell: ≥ 80% embryos<br>developed to expanded<br>blastocyst at 96 hours | 1-cell MEA % Expanded<br>blastocyst on day 5:<br>≥ 80 |
| Sterilization method | Aseptic filtration | Aseptic filtration |
| Storage conditions | Store dark at +2 to +8°C | Store dark at +2 to +8°C |
| Bottle | Nalgene PETG bottle with<br>HDPE closure and tamper<br>evident seal | Nalgene PETG bottle with<br>HDPE closure and tamper<br>evident seal |

intended use.

The subject and predicate device have different technological features, including different ingredients and specifications. The different technological characteristics, including composition and specifications, do not raise different questions of safety and effectiveness.

# 8. Summary of Non-Clinical Performance Testing

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

- . Aseptic filling validation study per ISO 13408-1:2008 and ISO 13408-2:2018
- Sterility testing per USP <71> (acceptance criterion: no microbial growth) .
- . Bacterial endotoxins testing per USP <85> (acceptance criterion: <0.25 EU/ml)
- pH measurements per USP <791> ●
- Osmolality per USP <785>
- Mouse Embryo Assay (MEA) using established protocol:

One-cell mouse embryos were cultured in test medium droplets. The percentage of embryos developed to the expanded blastocyst stage within 96 hours were assessed in comparison with the control group. The acceptance specification is "I-cell: ≥ 80% embryos developed to expanded blastocyst at 96 hours.

- . Shelf-life testing was conducted to ensure that the following product specifications are met at time zero and end of shelf-life: pH, osmolality, sterility, endotoxin, and 1-cell MEA.
- Open/close stability testing was conducted to ensure that the following product specifications are met at two weeks after opening of bottles: pH, osmolality sterility, endotoxin, and 1-cell MEA.
- Transportation testing was conducted according to ASTM D4169-16 to ensure that ● package integrity and device performance are maintained.
- Biocompatibility studies were performed on the patient-contacting devices as follows:

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- Cytotoxicity testing according to ISO 10993-5:2009 o
- Tests for Irritation and Skin Sensitization according to ISO 10993- O 10:2010, Guinea Pig Maximization Sensitization Test
- Tests for Irritation and Skin Sensitization according to ISO 10993o 10:2010, Vaginal Mucosal Irritation Study in Rabbits

The patient-contacting devices were shown to be non-cytotoxic, non-sensitizing, and nonirritating.

### 9. Conclusion

The nonclinical performance testing described above demonstrate that Gx-IVF™, Gx-TLTM, and Gx-MOPS™ PLUS are as safe and effective as the predicate devices and supports a determination of substantial equivalence.