FertiCult™ Flushing medium are intended for in vitro procedures involving human gametes (sperm and oocytes), including washing of gametes, sperm swim-up procedures, intra-uterine insemination (IUI) of the spermatozoa and sperm injection during intracytoplasmic sperm injection (ICSI). FertiCult™ Flushing medium can also be used human embryo washing and holding, and for embryo transfer (ET) in the uterine cavity. The medium is NOT intended for oocyte pick-up and follicle flushing. FertiCult Flushing medium is used during assisted reproductive Technology (ART) procedures of patients and couples undergoing infertility treatments.

Device Description

FertiCult Flushing medium and FertiCult Flushing medium with phenol red and gentamicin intended for in vitro procedures involving human gametes (sperm and oocytes), including washing of gametes, sperm swim-up procedures, intra-uterine insemination (IUI) of the spermatozoa and sperm injection during intracytoplasmic sperm injection (ICSI). FertiCult Flushing media can also be used for human embryo washing and holding, and for embryo transfer (ET) in the uterine cavity.

The base formulation contains Water, Sodium Chloride, Potassium Chloride, Calcium Chloride Dihydrate, Magnesium Sulphate Heptahydrate, Sodium Dihydrogen Phosphate Dihydrate, Sodium Pyruvate, Glucose Monohydrate, Sodium Lactate, Sodium hydrogen carbonate, HEPES, Human Serum Albumin.

A FertiCult Flushing media variant contains Phenol red and Gentamicin.

The products can be used up to 7 days after opening, when sterile conditions are maintained, and the products are stored at 2-8°C.

AI/ML Overview

The provided FDA 510(k) clearance letter pertains to the FertiCult Flushing medium and FertiCult Flushing medium with phenol red and gentamicin. This document demonstrates the substantial equivalence of the new device to a predicate device, as required for FDA clearance.

Here's an analysis of the acceptance criteria and the studies performed, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria listed are primarily for the physical, chemical, and biological properties of the media, ensuring its quality and suitability for use in Assisted Reproductive Technology (ART) procedures.

Acceptance Criteria	Reported Device Performance (from "Shelf-life testing" and "In-use testing")
Appearance	All solutions should be without precipitates (Met at Time 0, during shelf-life, and after 7 days of in-use testing)
pH (USP <791>)	7.3-7.9 (Met at Time 0, during shelf-life, and after 7 days of in-use testing)
Osmolality (USP <785>)	270-290 mOsmol/kg (Met at Time 0, during shelf-life, and after 7 days of in-use testing)
Sterility (USP <71>)	No microbial growth (Met at Time 0, during shelf-life, and after 7 days of in-use testing)
Bacterial Endotoxin (USP <85>)	< 0.25 EU/mL (Met at Time 0, during shelf-life, and after 7 days of in-use testing)
Mouse Embryo Assay (MEA)	One-Cell MEA: ≥ 80% embryos developed to expanded blastocyst at 96 hours after a 1-hour exposure to test medium (Met at Time 0, during shelf-life, and after 7 days of in-use testing)

Note: The document states that the product specifications were "met at time 0 and after real-time aging" for shelf-life, and "met seven days after opening" for in-use testing.

2. Sample Size Used for the Test Set and Data Provenance

The document does not explicitly state the specific sample sizes used for each test (e.g., how many batches were tested for pH, how many mouse embryos for MEA). It indicates that the tests were conducted for "validation and routine control" and to "support a shelf-life of 18 months" and "stability after bottle opening."

Regarding data provenance:

The studies are non-clinical performance tests conducted in support of substantial equivalence.
The data would originate from laboratory testing of the manufactured FertiCult media.
The document does not specify the country of origin of the data or whether it was retrospective or prospective, but given it's for a new product obtaining FDA clearance, it would be prospective testing of the device for submission.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

These types of tests (chemical assays, sterility, endotoxin, MEA, biocompatibility) do not typically involve human experts to establish "ground truth" in the way clinical studies often do. The "ground truth" is established by adherence to recognized scientific and regulatory standards (e.g., USP monographs, ISO standards, FDA guidance documents) by trained laboratory personnel. The document does not specify the number or qualifications of individuals performing these specific tests, but it can be assumed they are qualified laboratory technicians or scientists.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used in clinical studies with human interpretation (e.g., imaging reads). For the non-clinical laboratory tests described here, adjudication is not applicable. The results are quantitative measurements or qualitative observations (e.g., presence/absence of microbial growth, precipitates) interpreted against defined numerical or descriptive criteria set by the relevant standards.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. The provided document is for the premarket notification (510(k)) of a reproductive media product. MRMC studies are typically performed for diagnostic imaging devices or other devices where human interpretation is a key component and the AI system's impact on human performance is being evaluated. This document focuses on the safety and effectiveness of the media itself through laboratory and biocompatibility testing, not on human-AI interaction.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

No. This device is a culture medium, not an algorithm or AI-powered system. Therefore, standalone algorithm performance is not applicable.

7. The Type of Ground Truth Used

The ground truth for these non-clinical tests is based on:

Established scientific and regulatory standards: USP monographs (<791> for pH, <785> for Osmolality, <71> for Sterility, <85> for Bacterial Endotoxin), ISO standards (e.g., ISO 13408, ISO 11137, ISO 17665, ISO 10993 series), ASTM D4169-22.
Historically accepted biological performance indicators: Mouse Embryo Assay (MEA) results (development to expanded blastocyst), as specified by the 2021 FDA guidance.
Observed physical and chemical characteristics: Absence of precipitates.

These are objective, quantifiable, or universally accepted biological endpoints, rather than expert consensus on a subjective interpretation.

8. The Sample Size for the Training Set

Not applicable. This device is a culture medium, not an AI/ML algorithm that requires a training set. The performance testing described validates the manufacturing quality and biological compatibility of the product.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as this is not an AI/ML device requiring a training set.

Summary

U.S. Food & Drug Administration 510(k) Clearance Letter

Page 1

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.07.05

May 30, 2025

FertiPro NV
℅ Sarah Robbins
Senior Quality Manager, Consultant
Rock Quality Systems
1155 Mount Vernon Hwy Suite 800,
Dunwoody, GA 30338 USA

Re: K242640
Trade/Device Name: FertiCult Flushing medium; FertiCult Flushing medium with phenol red and gentamicin
Regulation Number: 21 CFR 884.6180
Regulation Name: Reproductive Media and Supplements
Regulatory Class: II
Product Code: MQL
Dated: March 5, 2024
Received: September 3, 2024

Dear Sarah Robbins:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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. 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 (reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-devices/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-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

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the DICE website (https://www.fda.gov/medical-devices/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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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120
Expiration Date: 06/30/2023
See PRA Statement below.

510(k) Number (if known)
K242640

Device Name
FertiCult Flushing medium; FertiCult Flushing medium with phenol red and gentamicin

Indications for Use (Describe)
FertiCult™ Flushing medium are intended for in vitro procedures involving human gametes (sperm and oocytes), including washing of gametes, sperm swim-up procedures, intra-uterine insemination (IUI) of the spermatozoa and sperm injection during intracytoplasmic sperm injection (ICSI). FertiCult™ Flushing medium can also be used human embryo washing and holding, and for embryo transfer (ET) in the uterine cavity. The medium is NOT intended for oocyte pick-up and follicle flushing. FertiCult Flushing medium is used during assisted reproductive Technology (ART) procedures of patients and couples undergoing infertility treatments.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

FORM FDA 3881 (6/20) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF

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510(k) Summary

K242640

I. SUBMITTER

Applicant: FertiPro NV
Address: Industriepark Noord 32, 8730 Beemem Belgium
Phone: (+32)50791805
Email: ra.@fertiPro.com
Contact Person: Liesbeth Faes, Management Representative FertiPro NV
Email: liesbeth@fertipro.com
Date Prepared: May 28, 2025

II. DEVICE

Trade Name: FertiCult Flushing medium; FertiCult Flushing medium with phenol red and gentamicin
Common Name: Assisted Reproduction Media
Regulation Name: Reproductive Media and Supplements
Regulation Number: 884.6180
Product Code: MQL (Media, Reproductive)
Regulatory Class: II

III. PREDICATE DEVICE

K983586 - HTF Medium, Modified HTF Medium-HEPES, HTF Powder (without antibiotics), Modified HTF Powder-HEPES (without antibiotics), Modified HTF Powder-HEPES from Irvine Scientific Sales Co., Inc.

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

IV. DEVICE DESCRIPTION

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A FertiCult Flushing media variant contains Phenol red and Gentamicin.

The products can be used up to 7 days after opening, when sterile conditions are maintained, and the products are stored at 2-8°C.

V. INDICATIONS FOR USE

VI. COMPARISON OF INTENDED USE AND TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

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

Comparison Item	K242640 Subject Device	K983586 Predicate Device	Comparison
Indications for Use	FertiCult™ Flushing medium are intended for in vitro procedures involving human gametes (sperm and oocytes), including washing of gametes, sperm swim-up procedures, intra-uterine insemination (IUI) of the spermatozoa and sperm injection during intracytoplasmic sperm injection	HTF and Modified HTF are intended for use in assisted reproductive technology procedures that involve the manipulation of gametes or embryos. Specifically, HTF is intended for use as a culture medium for the embryo after fertilization, when used with an	There are differences in the wording of the indications for use statements for the subject and predicate device; however,

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K242640
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Comparison Item	K242640 Subject Device	K983586 Predicate Device	Comparison
	(ICSI). FertiCult™ Flushing medium can also be used human embryo washing and holding, and for embryo transfer (ET) in the uterine cavity. The medium is NOT intended for oocyte pick-up and follicle flushing. FertiCult Flushing medium is used during assisted reproductive Technology (ART) procedures of patients and couples undergoing infertility treatments.	incubator, and as a medium to support in vitro fertilization. Modified HTF is intended for use as a sperm-processing medium in washing procedures, as an oocyte retrieval medium, for transport of the embryo, and as a support medium for implantation of the embryo. Both HTF and Modified HTF are intended to simulate the substances found in the human, female reproductive system.	the indications for use statements for the predicate device are similar in intended use for spermprocessing, sperm, oocyte, and embryo manipulation, embryo transfer.
Conditions for Use	Prescription Use Only	Prescription Use Only	Same
Composition	WaterSodium ChloridePotassium ChlorideCalcium Chloride DihydrateMagnesium Sulphate HeptahydrateSodium Dihydrogen Phosphate DihydrateSodium PyruvateGlucose MonohydrateSodium LactateSodium hydrogen carbonateHEPESHuman Serum AlbuminPhenol redGentamicin	WaterSodium-D, L-lactateSodium chloridePotassium chlorideGlucose anhydrousMagnesium sulfate, anhydrousPotassium phosphate, monobasicPyruvic acid, sodium saltCalcium chlorideHEPES ½ sodium saltHEPES sodium saltSodium hydrogen carbonateHydrogen chloride	Different: The subject device and predicate devices have differences in media formulation. These differences in composition do not raise different questions of safety and effectiveness (S&E).
pH	7.3-7.9	7.2-7.4	Different: The differences in pH

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Comparison Item	K242640 Subject Device	K983586 Predicate Device	Comparison
			specifications do not raise different questions of S&E.
Osmolality (mOsm/kg)	270-290 mOsmol/kg	Not available publicly	Different: The differences in osmolality specifications do not raise different questions of S&E.
Bacterial Endotoxin	<0.25 EU/mL	Not available publicly	Different: The differences in endotoxin specifications do not raise different questions of S&E.
Mouse Embryo Assay	One-Cell MEA: ≥ 80% embryos developed to expanded blastocyst at 96 hours after a 1-hour exposure to test medium	Not available publicly	Different: The differences in MEA specifications do not raise different questions of S&E.
Sterilization Method	Aseptic FiltrationVials are sterilized via radiation and moist heat	Not available publicly	Different: The differences in sterilization do not raise

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Comparison Item	K242640 Subject Device	K983586 Predicate Device	Comparison
			different questions of S&E.
Shelf-Life	18 months for medium in glass and 6 months for PETG bottles	Not available publicly	Different: The differences in shelf-life specifications do not raise different questions of S&E.

As shown in the table above, there are differences in the indications for use statements and technological characteristics of the subject and predicate devices. However, as stated in the table, the differences in indications for use do not represent a new intended use and the differences in technological characteristics do not raise different questions of safety and effectiveness.

VII. SUMMARY OF NON-CLINICAL PERFORMANCE TESTING

The following studies have been conducted in support of the substantial equivalence of the subject device to the predicate device.

Aseptic filtration and aseptic filling validation, per ISO 13408-1:2023, 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.
- For filter challenge test per ISO 13408-2, the solutions used for testing did not contain antimicrobials (gentamicin was excluded from subject media formulation) and were representative of worst-case production conditions.
PETG bottles radiation sterilization, per ISO 11137-1:2006 (including: Amendment 1 (2013) and Amendment 2 (2018)) Sterilization of health care products — Radiation — Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices and ISO 11137-2:2013 - Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose [Including Amendment 1 (2022)]. Glass bottles sterilized per ISO 17665-1:2006 Sterilization of

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health care products - Moist heat - Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices.

Shelf-life testing was conducted to support a shelf-life of 18 months for media in glass bottles and 6 months for media in PETG bottles through demonstration that the product specifications (shown below) were met at time 0 and after real time aging (at 20- 25°C for FertiCult Flushing medium and 2-8°C for FertiCult Flushing medium with phenol red and gentamicin):
- Appearance: All of the solutions should be without precipitates
- pH per USP <791>: 7.3-7.9
- Osmolality per USP <785>: 270-290 mOsmol/kg
- Sterility per USP <71>: No microbial growth
- Bacterial endotoxin per USP <85>: < 0.25 EU/mL
- MEA per the 2021 FDA guidance Mouse Embryo Assay for Assisted Reproduction Technology Devices:
  - One-Cell MEA: ≥ 80% embryos developed to expanded blastocyst at 96 hours after a 1-hour exposure to test medium
Transportation testing per ASTM D4169-22 (DC 13) and cap/seal leak testing using a method (dye immersion) equivalent to USP <1207.2> on transportation-conditioned devices.
In-use testing to support the stability after bottle opening to ensure that product specifications (as noted in shelf-life above) are met seven days after opening of the bottles.
Biocompatibility testing was conducted as the subject media is considered a device that contacts tissue with a limited (< 24 hours) contact duration as they can have direct contact with the patient (mother) during use in IUI and embryo transfer procedures Testing was conducted on FertiCult Flushing Media with phenol red and gentamicin (worst-case) in accordance with the 2023 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" and ISO 10993-1:2009 as follows:
- Cytotoxicity (ISO 10993-5:2009/(R)2014)
- Guinea Pig Maximization Sensitization Test (ISO 10993-10: 2021)
- Vaginal Irritation (ISO 10993-23: 2021)

The results of the testing conducted support the biocompatibility of the patient contacting subject devices.

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VIII. CONCLUSION

The results of the performance testing described above demonstrate that FertiCult Flushing medium; FertiCult Flushing medium with phenol red and gentamicin is as safe and effective as the predicate device and supports 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.